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Saou S, Moreau M, Lioret V, Berrou A, Hernandez-Garcia M, Decréau RA. Liposome: a tool to raise the Cherenkov radiation yield and to restore fluorophore properties in aqueous media. NANOSCALE 2025; 17:5429-5437. [PMID: 39898373 DOI: 10.1039/d4nr02605e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Liposomes used for the study were prepared and carefully characterized multiple times until all batches indicated the same characterization data (DOPC/cholesterol derivative (1 : 1.15 mol%), 14 mg(DOPC) mL-1, dDLS = 130 nm, 2 × 1011 liposome per nm3 of prepared batch, polydispersity index PDI = 0.1). The study shows that such a liposome suspension raises the yield in Cherenkov Radiation (CR) by 1.6-fold when in presence of [68Ga]-GaCl3, an efficient CR emitter (beta particle energy Eβ+ = 1800 KeV). Also, liposomes were found to prevent aggregation of a water-soluble phthalocyanine-pyranine PcPy4 dyad upon encapsulation, leading to its spectacular fluorescence restoration. Altogether, upon efficient 68Ga-radiolabelling of NODAGA-chelate immobilized at the liposome surface (99% radiolabelling yield, radio-TLC showed) encapsulating PcPy4 dyad (Caverage = 97 μM, Clumen = 300 μM), subsequent Cherenkov Radiation Energy Transfer (CRET) at the dyad antenna occurred. Internal energy transfers and fluorescence emission from the emitter dyad led to a 2.6-fold raise in radiance measured in the near-infrared (NIR) window (i.e. ca. 400 nm pseudo-Stokes shift). A similar raise in radiance was measured in the green window when encapsulation was achieved with eosin at the same rate. Liposome were found to be stable in PBS over 7 days regardless of the encapsulated fluorophore (no raise in dDLS diameter, no release of encapsulated dyes measured after Sephadex and FPLC repurification sequence), with some decay over 22 hours in a PBS/fetal calf serum mixture (1 : 1 vol.).
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Affiliation(s)
- Sébastien Saou
- Université de Bourgogne, ICMUB UMR CNRS 6302, 21000 Dijon, France.
| | - Mathieu Moreau
- Université de Bourgogne, ICMUB UMR CNRS 6302, 21000 Dijon, France.
| | - Vivian Lioret
- Université de Bourgogne, ICMUB UMR CNRS 6302, 21000 Dijon, France.
| | - Anne Berrou
- Université de Bourgogne, ICMUB UMR CNRS 6302, 21000 Dijon, France.
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Serafini D, Zancopè N, Pavone AM, Benfante V, Arzenton A, Russo V, Ballan M, Morselli L, Cammarata FP, Comelli A, Russo G, Scopelliti F, Di Marco V, Mastrotto F, Asti M, Maniglio D, Sbarra C, Bortolussi S, Donzella A, Zenoni A, Gandini A, Villa V, Paderno D, Zangrando L, Corradetti S, Mariotti E, Salvini A, Torrisi F, Lunardon M, Andrighetto A. 111Ag phantom images with Cerenkov Luminescence Imaging and digital autoradiography within the ISOLPHARM project. Appl Radiat Isot 2024; 215:111562. [PMID: 39488936 DOI: 10.1016/j.apradiso.2024.111562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 10/08/2024] [Accepted: 10/21/2024] [Indexed: 11/05/2024]
Abstract
Targeted Radionuclide Therapy (TRT) is a medical technique exploiting radionuclides to combat cancer growth and spread. TRT requires a supply of radionuclides that are currently produced by either cyclotrons or nuclear research reactors. In this context, the ISOLPHARM project investigates the production of innovative radionuclides for medical applications. This production will be based on the forthcoming SPES facility at the Legnaro National Laboratories (LNL) of the National Institute for Nuclear Physics (INFN), an ISOL facility where high-purity radioactive beams will be used to produce carrier-free radiopharmaceuticals. Previous studies demonstrated that a significant amount of 111Ag, an innovative β/γ emitter suitable for TRT with theranostic applications, can be obtained at the SPES facility. The present work describes the first imaging study on phantoms with 111Ag performed by the ISOLPHARM collaboration. This is a fundamental step to pave the way for the upcoming in vivo studies on the 111Ag-based radiopharmaceutical currently being developed. The imaging potential of this radionuclide was investigated by acquiring phantom images with Cerenkov Luminescence Imaging (CLI) and digital autoradiography (ARG).
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Affiliation(s)
- Davide Serafini
- Legnaro National Laboratories, National Institute for Nuclear Physics, INFN-LNL, Viale dell'Università 2, 35020 Legnaro, Italy; Department of Physical Sciences, Earth and Environment, University of Siena, Via Roma 56, 53100 Siena, Italy.
| | - Nicola Zancopè
- Department of Physics and Astronomy, University of Padova, Via Marzolo 8, 35131 Padova, Italy.
| | - Anna Maria Pavone
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy; Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy.
| | - Viviana Benfante
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy; Institute of Molecular Bioimaging and Physiology, National Research Council. IBFM-CNR, Contrada Pietrapollastra-Pisciotto, 90015 Cefalù, Italy.
| | - Alberto Arzenton
- Legnaro National Laboratories, National Institute for Nuclear Physics, INFN-LNL, Viale dell'Università 2, 35020 Legnaro, Italy; Department of Physical Sciences, Earth and Environment, University of Siena, Via Roma 56, 53100 Siena, Italy.
| | - Vincenzo Russo
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy.
| | - Michele Ballan
- Legnaro National Laboratories, National Institute for Nuclear Physics, INFN-LNL, Viale dell'Università 2, 35020 Legnaro, Italy.
| | - Luca Morselli
- Legnaro National Laboratories, National Institute for Nuclear Physics, INFN-LNL, Viale dell'Università 2, 35020 Legnaro, Italy; Department of Physics and Earth Science, University of Ferrara, Via G. Saragat 1, 44121 Ferrara, Italy.
| | - Francesco Paolo Cammarata
- Institute of Molecular Bioimaging and Physiology, National Research Council. IBFM-CNR, Contrada Pietrapollastra-Pisciotto, 90015 Cefalù, Italy; Laboratori Nazionali del Sud, National Institute for Nuclear Physics, INFN-LNS, Via Santa Sofia 62, 95123 Catania, Italy.
| | - Albert Comelli
- Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy.
| | - Giorgio Russo
- Institute of Molecular Bioimaging and Physiology, National Research Council. IBFM-CNR, Contrada Pietrapollastra-Pisciotto, 90015 Cefalù, Italy; Laboratori Nazionali del Sud, National Institute for Nuclear Physics, INFN-LNS, Via Santa Sofia 62, 95123 Catania, Italy.
| | - Fabrizio Scopelliti
- Nuclear Medicine Department of Cannizzaro Hospital, Via Messina 829, 95126 Catania, Italy.
| | - Valerio Di Marco
- Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy.
| | - Francesca Mastrotto
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
| | - Mattia Asti
- Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, AUSL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42122 Reggio Emilia, Italy.
| | - Devid Maniglio
- Department of Industrial Engineering, BIOtech Research Center, University of Trento, Via delle Regole 101, 38123 Mattarello, Italy.
| | - Carla Sbarra
- Bologna Division, National Institute for Nuclear Physics, Viale C. Berti Pichat 6/2, 40127 Bologna, Italy.
| | - Silva Bortolussi
- Department of Physics, University of Pavia, Via Bassi 6, 27100 Pavia, Italy.
| | - Antonietta Donzella
- Department of Mechanical and Industrial Engineering, University of Brescia, Via Branze 38, 25123 Brescia, Italy; Pavia Division, National Institute for Nuclear Physics, Via Bassi 6, 27100 Pavia, Italy.
| | - Aldo Zenoni
- Department of Mechanical and Industrial Engineering, University of Brescia, Via Branze 38, 25123 Brescia, Italy; Pavia Division, National Institute for Nuclear Physics, Via Bassi 6, 27100 Pavia, Italy.
| | - Andrea Gandini
- Applied Nuclear Energy Laboratory, LENA, Via G. Aselli 41, 27100 Pavia, Italy.
| | - Valerio Villa
- Department of Mechanical and Industrial Engineering, University of Brescia, Via Branze 38, 25123 Brescia, Italy; Pavia Division, National Institute for Nuclear Physics, Via Bassi 6, 27100 Pavia, Italy.
| | - Diego Paderno
- Department of Mechanical and Industrial Engineering, University of Brescia, Via Branze 38, 25123 Brescia, Italy; Pavia Division, National Institute for Nuclear Physics, Via Bassi 6, 27100 Pavia, Italy.
| | - Lisa Zangrando
- Padova Division, National Institute for Nuclear Physics, Via Marzolo 8, 35131 Padova, Italy.
| | - Stefano Corradetti
- Legnaro National Laboratories, National Institute for Nuclear Physics, INFN-LNL, Viale dell'Università 2, 35020 Legnaro, Italy.
| | - Emilio Mariotti
- Department of Physical Sciences, Earth and Environment, University of Siena, Via Roma 56, 53100 Siena, Italy; Pisa Division, National Institute for Nuclear Physics, Largo Bruno Pontecorvo 3, 56127 Pisa, Italy.
| | - Andrea Salvini
- Applied Nuclear Energy Laboratory, LENA, Via G. Aselli 41, 27100 Pavia, Italy.
| | - Filippo Torrisi
- Department of Medicine and Surgery, University of Enna "Kore", Via Marzolo 8, 35131 Enna, Italy.
| | - Marcello Lunardon
- Department of Physics and Astronomy, University of Padova, Via Marzolo 8, 35131 Padova, Italy; Padova Division, National Institute for Nuclear Physics, Via Marzolo 8, 35131 Padova, Italy.
| | - Alberto Andrighetto
- Legnaro National Laboratories, National Institute for Nuclear Physics, INFN-LNL, Viale dell'Università 2, 35020 Legnaro, Italy.
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Boykoff N, Grimm J. Current clinical applications of Cerenkov luminescence for intraoperative molecular imaging. Eur J Nucl Med Mol Imaging 2024; 51:2931-2940. [PMID: 38243119 PMCID: PMC11784920 DOI: 10.1007/s00259-024-06602-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 01/04/2024] [Indexed: 01/21/2024]
Abstract
BACKGROUND Cerenkov luminescence imaging (CLI) is a new emerging technology that can be used for optical imaging of approved radiotracers, both in a preclinical, and even more recently, in a clinical context with rapid imaging times, low costs, and detection in real-time (Grootendorst et al. Clin Transl Imaging 4(5):353-66, 2016); Wang et al. Photonics 9(6):390, 2022). This brief review provides an overview of clinical applications of CLI with a focus on intraoperative margin assessment (IMA) to address shortcomings and provide insight for future work in this application. METHODS A literature review was performed using PubMed using the search words Cerenkov luminescence imaging (CLI), intraoperative margin assessment (IMA), and image-guided surgery. Articles were selected based on title, abstract, content, and application. RESULTS Original research was summarized to examine advantages and limitations of CLI compared to other modalities for IMA. The characteristics of Cerenkov luminescence (CL) are defined, and results from relevant clinical trials are discussed. Prospects of ongoing clinical trials are reviewed, along with technological advancements related to CLI. CONCLUSION CLI is a proven method for molecular imaging and shows feasibility for determining intraoperative margins if future work involves establishing quantitative approaches for attenuation and scattering, depth analysis, and radiation safety for CLI at a larger scale.
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Affiliation(s)
- Natalie Boykoff
- Department of Chemistry and Biochemistry, The City College of New York, 160 Convent Avenue, New York, NY, 10031, USA
- Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY, 10016, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Jan Grimm
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
- Pharmacology Program, Weill Cornell Medical College, New York, NY, 10021, USA.
- Department of Radiology, Weill Cornell Medical College, New York, NY, 10021, USA.
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Fragoso Costa P, Shi K, Holm S, Vidal-Sicart S, Kracmerova T, Tosi G, Grimm J, Visvikis D, Knapp WH, Gnanasegaran G, van Leeuwen FWB. Surgical radioguidance with beta-emitting radionuclides; challenges and possibilities: A position paper by the EANM. Eur J Nucl Med Mol Imaging 2024; 51:2903-2921. [PMID: 38189911 PMCID: PMC11300492 DOI: 10.1007/s00259-023-06560-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 12/01/2023] [Indexed: 01/09/2024]
Abstract
Radioguidance that makes use of β-emitting radionuclides is gaining in popularity and could have potential to strengthen the range of existing radioguidance techniques. While there is a strong tendency to develop new PET radiotracers, due to favorable imaging characteristics and the success of theranostics research, there are practical challenges that need to be overcome when considering use of β-emitters for surgical radioguidance. In this position paper, the EANM identifies the possibilities and challenges that relate to the successful implementation of β-emitters in surgical guidance, covering aspects related to instrumentation, radiation protection, and modes of implementation.
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Affiliation(s)
- Pedro Fragoso Costa
- Department of Nuclear Medicine, University Hospital Essen, West German Cancer Center (WTZ), University of Duisburg-Essen, Essen, Germany.
| | - Kuangyu Shi
- Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Computer Aided Medical Procedures and Augmented Reality, Institute of Informatics I16, Technical University of Munich, Munich, Germany
| | - Soren Holm
- Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital Copenhagen, Copenhagen, Denmark
| | - Sergi Vidal-Sicart
- Nuclear Medicine Department, Hospital Clinic Barcelona, Barcelona, Spain
| | - Tereza Kracmerova
- Department of Medical Physics, Motol University Hospital, Prague, Czech Republic
| | - Giovanni Tosi
- Department of Medical Physics, Ospedale U. Parini, Aosta, Italy
| | - Jan Grimm
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Wolfram H Knapp
- Department of Nuclear Medicine, Medizinische Hochschule Hannover, Hannover, Germany
| | - Gopinath Gnanasegaran
- Institute of Nuclear Medicine, University College London Hospital, Tower 5, 235 Euston Road, London, NW1 2BU, UK
- Royal Free London NHS Foundation Trust Hospital, London, UK
| | - Fijs W B van Leeuwen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
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Morrison A, Srivatsa VM, Ghandi K. Superluminal Molecular and Nanomaterial Probes Based on Fast Ions or Electrons. Molecules 2024; 29:2903. [PMID: 38930968 PMCID: PMC11206977 DOI: 10.3390/molecules29122903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 06/06/2024] [Accepted: 06/09/2024] [Indexed: 06/28/2024] Open
Abstract
This work reviews the progression of chemical analysis via Cherenkov emissions, i.e., Cherenkov Photometry and Cherenkov Emission Spectroscopy, from its introduction in the literature up to modern developments. In presenting the history of this field, we aim to consolidate the literature, both for reference and contextualization. We present an argument aiming to untangle why this corner of research has seen little progress while so many other directly related aspects of Cherenkov research have flourished, as well as speak to the progress of the field in recent years and prospective direction in years to come.
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Affiliation(s)
| | | | - Khashayar Ghandi
- Department of Chemistry, University of Guelph, 50 Stone Road East, Guelph, ON N1G 2W1, Canada; (A.M.); (V.M.S.)
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6
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Teng M, Liang X, Liu H, Li Z, Gao X, Zhang C, Cheng H, Chen H, Liu G. Cerenkov radiation shining a light for cancer theranostics. NANO TODAY 2024; 55:102174. [DOI: 10.1016/j.nantod.2024.102174] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
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Mc Veigh M, Bellan LM. Microfluidic synthesis of radiotracers: recent developments and commercialization prospects. LAB ON A CHIP 2024; 24:1226-1243. [PMID: 38165824 DOI: 10.1039/d3lc00779k] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
Positron emission tomography (PET) is a powerful diagnostic tool that holds incredible potential for clinicians to track a wide variety of biological processes using specialized radiotracers. Currently, however, a single radiotracer accounts for over 95% of procedures, largely due to the cost of radiotracer synthesis. Microfluidic platforms provide a solution to this problem by enabling a dose-on-demand pipeline in which a single benchtop platform would synthesize a wide array of radiotracers. In this review, we will explore the field of microfluidic production of radiotracers from early research to current development. Furthermore, the benefits and drawbacks of different microfluidic reactor designs will be analyzed. Lastly, we will discuss the various engineering considerations that must be addressed to create a fully developed, commercially effective platform that can usher the field from research and development to commercialization.
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Affiliation(s)
- Mark Mc Veigh
- Interdisciplinary Materials Science Program, Vanderbilt University, Nashville, TN, 37235, USA
| | - Leon M Bellan
- Department of Mechanical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA
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8
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Ran C, Pu K. Molecularly generated light and its biomedical applications. Angew Chem Int Ed Engl 2024; 63:e202314468. [PMID: 37955419 DOI: 10.1002/anie.202314468] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/01/2023] [Accepted: 11/10/2023] [Indexed: 11/14/2023]
Abstract
Molecularly generated light, referred to here as "molecular light", mainly includes bioluminescence, chemiluminescence, and Cerenkov luminescence. Molecular light possesses unique dual features of being both a molecule and a source of light. Its molecular nature enables it to be delivered as molecules to regions deep within the body, overcoming the limitations of natural sunlight and physically generated light sources like lasers and LEDs. Simultaneously, its light properties make it valuable for applications such as imaging, photodynamic therapy, photo-oxidative therapy, and photobiomodulation. In this review article, we provide an updated overview of the diverse applications of molecular light and discuss the strengths and weaknesses of molecular light across various domains. Lastly, we present forward-looking perspectives on the potential of molecular light in the realms of molecular imaging, photobiological mechanisms, therapeutic applications, and photobiomodulation. While some of these perspectives may be considered bold and contentious, our intent is to inspire further innovations in the field of molecular light applications.
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Affiliation(s)
- Chongzhao Ran
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
| | - Kanyi Pu
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 637459, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore, Singapore
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9
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Aung W, Tsuji AB, Rikiyama K, Nishikido F, Obara S, Higashi T. Imaging assessment of photosensitizer emission induced by radionuclide-derived Cherenkov radiation using charge-coupled device optical imaging and long-pass filters. World J Radiol 2023; 15:315-323. [PMID: 38058603 PMCID: PMC10696188 DOI: 10.4329/wjr.v15.i11.315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/26/2023] [Accepted: 11/17/2023] [Indexed: 11/24/2023] Open
Abstract
BACKGROUND Radionuclides produce Cherenkov radiation (CR), which can potentially activate photosensitizers (PSs) in phototherapy. Several groups have studied Cherenkov energy transfer to PSs using optical imaging; however, cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge. Many laboratories face the need for expensive dedicated equipment. AIM To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs. METHODS The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs. To mitigate the need for expensive dedicated equipment and achieve the aim of the study, we developed a method that utilizes a charge-coupled device optical imaging system and appropriate long-pass filters of different wavelengths (manual sequential application of long-pass filters of 515, 580, 645, 700, 750, and 800 nm). Tetrakis (4-carboxyphenyl) porphyrin (TCPP) was utilized as a model PS. Different doses of copper-64 (64CuCl2) (4, 2, and 1 mCi) were used as CR-producing radionuclides. Imaging and data acquisition were performed 0.5 h after sample preparation. Differential image analysis was conducted by using ImageJ software (National Institutes of Health) to visually evaluate TCPP fluorescence. RESULTS The maximum absorbance of TCPP was at 390-430 nm, and the emission peak was at 670 nm. The CR and CR-induced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above. The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity (total flux) difference between 64CuCl2 + TCPP and 64CuCl2. Moreover, the differential fluorescence images of TCPP were obtained by subtracting the 64CuCl2 image from the 64CuCl2 + TCPP image. The experimental results considering different 64CuCl2 doses showed a dose-dependent trend. These results demonstrate that a bioluminescence imaging device coupled with different long-pass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP. CONCLUSION This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.
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Affiliation(s)
- Winn Aung
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Atsushi B Tsuji
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Kazuaki Rikiyama
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Fumihiko Nishikido
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Satoshi Obara
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Tatsuya Higashi
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
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10
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Zhang X, Li J, Wang T, Liu N, Su X. Cerenkov radiation-mediated in situ activation of silicon nanocrystals for NIR optical imaging. Chem Commun (Camb) 2023; 59:13990-13992. [PMID: 37937992 DOI: 10.1039/d3cc04468h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2023]
Abstract
Cerenkov radiation from radiopharmaceuticals (18F-FDG) serves as an internal light source to excite UV-responsive silicon nanocrystals for near-infrared luminescence imaging that offers deeper tissue penetration and high signal-to-noise ratio.
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Affiliation(s)
- Xun Zhang
- PET Center, Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
- School of Medicine, Xiamen University, Xiamen 361005, China
| | - Jingchao Li
- PET Center, Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
| | - Tingting Wang
- PET Center, Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
- School of Medicine, Xiamen University, Xiamen 361005, China
| | - Nian Liu
- PET Center, Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
| | - Xinhui Su
- PET Center, Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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11
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Cui X, Li X, Peng C, Qiu Y, Shi Y, Liu Y, Fei JF. Beyond External Light: On-Spot Light Generation or Light Delivery for Highly Penetrated Photodynamic Therapy. ACS NANO 2023; 17:20776-20803. [PMID: 37874930 DOI: 10.1021/acsnano.3c05619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2023]
Abstract
External light sources, such as lasers, light emitting diodes (LEDs) and lamps, are widely applied in photodynamic therapy (PDT); however, their use is severely limited by the nature of shallow tissue penetration depth. The recent exploration of light delivery or local generation on tumor sites has attracted much attention, owing to the fact that these systems are significantly endowed with high tissue penetration. In this review, we briefly introduced the principle of "on-spot light generation or delivery systems" in PDT. These systems are divided into different categories: (1) implantable luminescence, (2) mechanoluminescence, (3) electrochemiluminescence, (4) Cerenkov luminescence, (5) chemiluminescence, and (6) bioluminescence. Finally, their applications, advantages, and disadvantages in PDT will be appropriately summarized and further discussed in detail. We believe that this review will provide general guidance for the further design of light generation or delivery systems and clinical studies for PDT-mediated cancer treatments with unparalleled merits.
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Affiliation(s)
- Xiao Cui
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, People's Republic of China
- Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Xiang Li
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, People's Republic of China
- Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Cheng Peng
- Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China, Institute for Brain Research and Rehabilitation, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, 510631, People's Republic of China
| | - Yuanhui Qiu
- Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China, Institute for Brain Research and Rehabilitation, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, 510631, People's Republic of China
| | - Yu Shi
- Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China, Institute for Brain Research and Rehabilitation, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, 510631, People's Republic of China
| | - Yanmei Liu
- Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, China, Institute for Brain Research and Rehabilitation, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, 510631, People's Republic of China
| | - Ji-Feng Fei
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, People's Republic of China
- Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, People's Republic of China
- School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, People's Republic of China
- School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, People's Republic of China
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12
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Rosenkrans ZT, Hsu JC, Aluicio-Sarduy E, Barnhart TE, Engle JW, Cai W. Amplification of Cerenkov luminescence using semiconducting polymers for cancer theranostics. ADVANCED FUNCTIONAL MATERIALS 2023; 33:2302777. [PMID: 37942189 PMCID: PMC10629852 DOI: 10.1002/adfm.202302777] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Indexed: 11/10/2023]
Abstract
The therapeutic efficacy of photodynamic therapy is limited by the ability of light to penetrate tissues. Due to this limitation, Cerenkov luminescence (CL) from radionuclides has recently been proposed as an alternative light source in a strategy referred to as Cerenkov radiation induced therapy (CRIT). Semiconducting polymer nanoparticles (SPNs) have ideal optical properties, such as large absorption cross-sections and broad absorbance, which can be utilized to harness the relatively weak CL produced by radionuclides. SPNs can be doped with photosensitizers and have nearly 100% energy transfer efficiency by multiple energy transfer mechanisms. Herein, we investigated an optimized photosensitizer doped SPN as a nanosystem to harness and amplify CL for cancer theranostics. We found that semiconducting polymers significantly amplified CL energy transfer efficiency. Bimodal PET and optical imaging studies showed high tumor uptake and retention of the optimized SPNs when administered intravenously or intratumorally. Lastly, we found that photosensitizer doped SPNs have excellent potential as a cancer theranostics nanosystem in an in vivo tumor therapy study. Our study shows that SPNs are ideally suited to harness and amplify CL for cancer theranostics, which may provide a significant advancement for CRIT that are unabated by tissue penetration limits.
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Affiliation(s)
- Zachary T Rosenkrans
- University of Wisconsin-Madison, Department of Pharmaceutical Sciences, 600 Highland Ave., K6/562, Madison, WI 53792, USA
| | - Jessica C Hsu
- University of Wisconsin-Madison, Departments of Radiology and Medical Physics, Madison, WI 53705, USA
| | - Eduardo Aluicio-Sarduy
- University of Wisconsin-Madison, Departments of Radiology and Medical Physics, Madison, WI 53705, USA
| | - Todd E Barnhart
- University of Wisconsin-Madison, Departments of Radiology and Medical Physics, Madison, WI 53705, USA
| | - Jonathan W Engle
- University of Wisconsin-Madison, Departments of Radiology and Medical Physics, Madison, WI 53705, USA
- University of Wisconsin-Madison, Carbone Cancer Center, Madison, WI 53705, USA
| | - Weibo Cai
- University of Wisconsin-Madison, Department of Pharmaceutical Sciences, 600 Highland Ave., K6/562, Madison, WI 53792, USA
- University of Wisconsin-Madison, Departments of Radiology and Medical Physics, Madison, WI 53705, USA
- University of Wisconsin-Madison, Carbone Cancer Center, Madison, WI 53705, USA
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13
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Cao X, Li W, Chen Y, Du M, Zhang G, Zhang J, Li K, Su L. K-CapsNet: K-Nearest Neighbor Based Convolution Capsule Network for Cerenkov Luminescence Tomography Reconstruction. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2023; 2023:1-4. [PMID: 38082846 DOI: 10.1109/embc40787.2023.10341089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
Cerenkov luminescence tomography (CLT) has received significant attention as a promising imaging modality that can display the three-dimensional (3D) distribution of radioactive probes. However, the reconstruction of CLT suffers from severe ill-posed problem. It is difficult for traditional model-based method to obtain satisfactory result. Recently, deep learning-based method have shown great potential for accurate and efficient CLT reconstruction. In this study, a KNN-based convolution capsule network, named K-CapsNet, is proposed for cerenkov luminescence tomography. In K-CapsNet, the surface photon intensity is encoded in capsule form. The KNN-based convolution and K-means clustering are proposed for efficient encoding. Numerical simulation experiments have been carried out to verify the performance of K-CapsNet, and the results show that it performs superior in source localization and morphological restoration compared with existing methods.
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14
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Practical Guidance for Developing Small-Molecule Optical Probes for In Vivo Imaging. Mol Imaging Biol 2023; 25:240-264. [PMID: 36745354 DOI: 10.1007/s11307-023-01800-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 12/31/2022] [Accepted: 01/05/2023] [Indexed: 02/07/2023]
Abstract
The WMIS Education Committee (2019-2022) reached a consensus that white papers on molecular imaging could be beneficial for practitioners of molecular imaging at their early career stages and other scientists who are interested in molecular imaging. With this consensus, the committee plans to publish a series of white papers on topics related to the daily practice of molecular imaging. In this white paper, we aim to provide practical guidance that could be helpful for optical molecular imaging, particularly for small molecule probe development and validation in vitro and in vivo. The focus of this paper is preclinical animal studies with small-molecule optical probes. Near-infrared fluorescence imaging, bioluminescence imaging, chemiluminescence imaging, image-guided surgery, and Cerenkov luminescence imaging are discussed in this white paper.
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15
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Pratt EC, Shaffer TM, Bauer D, Lewis JS, Grimm J. Radiances of Cerenkov-Emitting Isotopes on the IVIS. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.18.524625. [PMID: 36711894 PMCID: PMC9882406 DOI: 10.1101/2023.01.18.524625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Cerenkov (or Cherenkov) luminescence occurs when charged particles exceed the phase velocity of a given medium. Cerenkov has gained interest in preclinical space as well as in clinical trials for optical visualization of numerous radionuclides. However, Cerenkov intensity has to be inferred from alternative databases with energy emission spectra, or theoretical fluence estimates. Here we present the largest experimental dataset of Cerenkov emitting isotopes recorded using the IVIS optical imaging system. We report Cerenkov measurements spanning orders of magnitude normalized to the activity concentration for 21 Cerenkov emitting isotopes, covering electron, alpha, beta minus, and positron emissions. Isotopes measured include Carbon-11, Fluorine-18, Phosphorous-32, Scandium-47, Copper-64, Copper-67, Gallium-68, Arsenic-72, Bromine-76, Yttrium-86, Zirconium-89, Yttrium-90, Iodine-124, Iodine-131, Cerium-134, Lutetium-177, Lead-203, Lead-212, Radium-223, Actinium-225, and Thorium-227. We hope this updating resource will serve as a rank ordering for comparing isotopes for Cerenkov luminescence in the visible window and serve as a rule of thumb for comparing Cerenkov intensities in vitro and in vivo. Methods All Cerenkov emitting radionuclides were either produced at Memorial Sloan Kettering Cancer Center (Carbon-11, 11 C; Fluorine-18, 18 F; Iodine-124, 124 I), from commercial sources such as Perkin Elmer (Phosphorous-32, 32 P; Yttrium-90, 90 Y), Bayer (Radium-223, 223 Ra, Xofigo), 3D-Imaging (Zirconium-89, 89 Zr), Nuclear Diagnostic Products (Iodine-131, 131 I), or from academic collaborators at Washington University at St. Louis (Copper-64, 64 Cu), University of Wisconsin (Bromine-76, 76 Br), MD Anderson Cancer Center (Yttrium-86, 86 Y), Brookhaven National Laboratory (Arsenic-72, 72 As; Thorium-227, 227 Th), or Oak Ridge National Laboratory (Cerium-134, 134 Ce, Actinium-225, 225 Ac), and Viewpoint Molecular Targeting (Lead-203, 203 Pb; Lead 212, 212 Pb). All isotopes were diluted in triplicate on a black bottomed corning 96 well plate to several activity concentrations ranging from 0.1-250 μCi in 100-200 μL of Phosphate Buffered Saline. Cerenkov imaging was acquired on a single Perkin-Elmer Spectrum In-Vivo Imaging System (IVIS) at field of view c with exposures ranging up to 15 minutes or lower provided no part of the image intensity was saturated, or that the activity significantly changed during the exposure. Experimental radiances on the IVIS were calculated from regions of interest drown over each 96 well, and then normalized for the activity present in the well, and the volume the isotope was diluted into.
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16
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Guo R, Jiang D, Gai Y, Qian R, Zhu Z, Gao Y, Jing B, Yang B, Lan X, An R. Chlorin e6-loaded goat milk-derived extracellular vesicles for Cerenkov luminescence-induced photodynamic therapy. Eur J Nucl Med Mol Imaging 2023; 50:508-524. [PMID: 36222853 DOI: 10.1007/s00259-022-05978-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 09/16/2022] [Indexed: 01/11/2023]
Abstract
PURPOSE Photodynamic therapy (PDT) is a promising cancer treatment strategy with rapid progress in preclinical and clinical settings. However, the limitations in penetration of external light and precise delivery of photosensitizers hamper its clinical translation. As such, the internal light source such as Cerenkov luminescence (CL) from decaying radioisotopes offers new opportunities. Herein, we show that goat milk-derived extracellular vesicles (GEV) can act as a carrier to deliver photosensitizer Chlorin e6 (Ce6) and tumor-avid 18F-FDG can activate CL-induced PDT for precision cancer theranostics. METHODS GEV was isolated via differential ultracentrifugation of commercial goat milk and photosensitizer Ce6 was loaded by co-incubation to obtain Ce6@GEV. Tumor uptake of Ce6@GEV was examined using confocal microscopy and flow cytometry. To demonstrate the ability of 18F-FDG to activate photodynamic effects against cancer cells, apoptosis rates were measured using flow cytometry, and the production of 1O2 was measured by reactive oxygen species (ROS) monitoring kit. Moreover, we used the IVIS device to detect Cherenkov radiation and Cerenkov radiation energy transfer (CRET). For animal experiments, a small-animal IVIS imaging system was used to visualize the accumulation of the GEV drug delivery system in tumors. PET/CT and CL images of the tumor site were performed at 0.5, 1, and 2 h. For in vivo antitumor therapy, changes of tumor volume, survival time, and body weight in six groups of tumor-bearing mice were monitored. Furthermore, the blood sample and organs of interest (heart, liver, spleen, lungs, kidneys, and tumor) were collected for hematological analysis, immunohistochemistry, and H&E staining. RESULTS Confocal microscopy of 4T1 cells incubated with Ce6@GEV for 4 h revealed strong red fluorescence signals in the cytoplasm, which demonstrated that Ce6 loaded in GEV could be efficiently delivered into tumor cells. When Ce6@GEV and 18F-FDG co-existed incubated with 4T1 cells, the cell viability plummeted from more than 88.02 ± 1.30% to 23.79 ± 1.59%, indicating excellent CL-induced PDT effects. In vivo fluorescence images showed a peak tumor/liver ratio of 1.36 ± 0.09 at 24 h after Ce6@GEV injection. For in vivo antitumor therapy, Ce6@GEV + 18F-FDG group had the best tumor inhibition rate (58.02%) compared with the other groups, with the longest survival rate (35 days, 40%). During the whole treatment process, neither blood biochemical analysis nor histological observation revealed vital organ damage, suggesting the biosafety of this treatment strategy. CONCLUSIONS The simultaneous accumulation of 18F-FDG and Ce6 in tumor tissues is expected to overcome the deficiency of traditional PDT. This strategy has the potential to extend PDT to a variety of tumors, including metastases, using targeted radiotracers to provide internal excitation of light-responsive therapeutics. We expect that our method will play a critical role in precision treatment of deep solid tumors.
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Affiliation(s)
- Rong Guo
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China
| | - Dawei Jiang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China
| | - Yongkang Gai
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China
| | - Ruijie Qian
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China
| | - Ziyang Zhu
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China
| | - Yu Gao
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China
| | - Boping Jing
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China
- Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Biao Yang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China
| | - Xiaoli Lan
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China.
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China.
| | - Rui An
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China.
- Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
- Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China.
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17
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Advanced techniques for performing photodynamic therapy in deep-seated tissues. Biomaterials 2022; 291:121875. [PMID: 36335717 DOI: 10.1016/j.biomaterials.2022.121875] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 10/07/2022] [Accepted: 10/23/2022] [Indexed: 11/23/2022]
Abstract
Photodynamic therapy (PDT) is a promising localized cancer treatment modality. It has been used successfully to treat a range of dermatological conditions with comparable efficacy to conventional treatments. However, some drawbacks limit the clinical utility of PDT in treating deep-seated tumors. Notably, the penetration limitation of UV and visible light, commonly applied to activate photosensitizers, makes PDT incompetent in treating deep-seated tumors. Development in light delivery technologies, especially fiber optics, led to improved clinical strategies for accessing deep tissues for irradiation. However, PDT efficacy issues remained partly due to light penetration limitations. In this review, we first summarized the current PDT applications for deep-seated tumor treatment. Then, the most recent progress in advanced techniques to overcome the light penetration limitation in PDT, including using functional nanomaterials that can either self-illuminate or be activated by near-infrared (NIR) light and X-rays as transducers, and implantable light delivery devices were discussed. Finally, current challenges and future opportunities of these technologies were discussed, which we hope may inspire the development of more effective techniques to enhance PDT efficacy against deep-seated tumors.
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18
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Liu N, Su X, Sun X. Cerenkov radiation-activated probes for deep cancer theranostics: a review. Theranostics 2022; 12:7404-7419. [PMID: 36438500 PMCID: PMC9691350 DOI: 10.7150/thno.75279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 09/07/2022] [Indexed: 11/05/2022] Open
Abstract
Cerenkov radiation (CR) from radionuclides and megavoltage X-ray radiation can act as an in situ light source for deep cancer theranostics, overcoming the limitations of external light sources. Despite the blue-weighted emission and low quantum yield of CR, activatable probes-mediated CR can enhance the in-vivo diagnostic signals by Cerenkov resonance energy transfer and also can produce therapeutic effects by reactive species generation/drug release, greatly promoting the biomedical applications of CR. In this review, we describe the principles and sources of CR, construction of CR-activated probes and their application to tumor optical imaging and therapy. Finally, future prospects for the design and biomedical application of CR-activated probes are discussed.
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Affiliation(s)
- Nian Liu
- PET Center, Department of Nuclear Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xinhui Su
- PET Center, Department of Nuclear Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xiaolian Sun
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China
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19
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Lee SY, Oh HR, Kim YH, Bae SH, Lee Y, Lee YS, Lee BC, Cheon GJ, Kang KW, Youn H. Cerenkov luminescence imaging of interscapular brown adipose tissue using a TSPO-targeting PET probe in the UCP1 ThermoMouse. Am J Cancer Res 2022; 12:6380-6394. [PMID: 36168637 PMCID: PMC9475450 DOI: 10.7150/thno.74828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 08/20/2022] [Indexed: 11/21/2022] Open
Abstract
Rationale: [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) has been widely used as an imaging technique to measure interscapular brown adipose tissue (iBAT) activity. However, it is challenging to obtain iBAT-specific images using [18F]FDG-PET because increased uptake of [18F]FDG is observed in tumors, muscle, and inflamed tissues. Uncoupling protein 1 (UCP1) in the mitochondrial membrane, a well-known molecular marker of BAT, has been proposed as a useful BAT imaging marker. Recently, the UCP1 ThermoMouse was developed as a reporter mouse for monitoring UCP1 expression and investigating BAT activation. In addition, Translocator protein-18 kDa (TSPO) located in the outer mitochondrial membrane is also overexpressed in BAT, suggesting that TSPO-targeting PET has potential for iBAT imaging. However, there are no studies monitoring BAT using TSPO-targeting PET probes in the UCP1 ThermoMouse. Moreover, the non-invasive Cerenkov luminescence imaging (CLI) using Cerenkov radiation from the PET probe has been proposed as an alternative option for PET as it is less expensive and user-friendly. Therefore, we selected [18F]fm-PBR28-d2 as a TSPO-targeting PET probe for iBAT imaging to evaluate the usefulness of CLI in the UCP1 ThermoMouse. Methods: UCP1 ThermoMouse was used to monitor UCP1 expression. Western blotting and immunohistochemistry were performed to measure the level of protein expression. [18F]fm-PBR28-d2 and [18F]FDG were used as radioactive probes for iBAT imaging. PET images were acquired with SimPET, and optical images were acquired with IVIS 100. Results: UCP1 ThermoMouse showed that UCP1 and TSPO expressions were correlated in iBAT. In both PET and CLI, the TSPO-targeting probe [18F]fm-PBR28-d2 was superior to [18F]FDG for acquiring iBAT images. The high molar activity of the probe was essential for CLI and PET imaging. We tested the feasibility of TSPO-targeting probe under cold exposure by imaging with TSPO-PET/CLI. Both signals of iBAT were clearly increased after cold stimulation. Under prolonged isoflurane anesthesia, TSPO-targeting images showed higher signals from iBAT in the short-term than in long-term groups. Conclusion: We demonstrated that TSPO-PET/CLI reflected UCP1 expression in iBAT imaging better than [18F]FDG-PET/CLI under the various conditions. Considering convenience and cost, TSPO-CLI could be used as an alternative TSPO-PET technique for iBAT imaging.
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Affiliation(s)
- Seok-Yong Lee
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Rim Oh
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young-Hwa Kim
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sung-Hwan Bae
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yongseok Lee
- Cancer Imaging Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yun-Sang Lee
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cancer Imaging Center, Seoul National University Hospital, Seoul, Republic of Korea.,Radiation Medicine Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Byung Chul Lee
- Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.,Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea
| | - Gi Jeong Cheon
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Keon Wook Kang
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyewon Youn
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cancer Imaging Center, Seoul National University Hospital, Seoul, Republic of Korea
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20
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Sarrut D, Arbor N, Baudier T, Borys D, Etxebeste A, Fuchs H, Gajewski J, Grevillot L, Jan S, Kagadis GC, Kang HG, Kirov A, Kochebina O, Krzemien W, Lomax A, Papadimitroulas P, Pommranz C, Roncali E, Rucinski A, Winterhalter C, Maigne L. The OpenGATE ecosystem for Monte Carlo simulation in medical physics. Phys Med Biol 2022; 67:10.1088/1361-6560/ac8c83. [PMID: 36001985 PMCID: PMC11149651 DOI: 10.1088/1361-6560/ac8c83] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 08/24/2022] [Indexed: 11/12/2022]
Abstract
This paper reviews the ecosystem of GATE, an open-source Monte Carlo toolkit for medical physics. Based on the shoulders of Geant4, the principal modules (geometry, physics, scorers) are described with brief descriptions of some key concepts (Volume, Actors, Digitizer). The main source code repositories are detailed together with the automated compilation and tests processes (Continuous Integration). We then described how the OpenGATE collaboration managed the collaborative development of about one hundred developers during almost 20 years. The impact of GATE on medical physics and cancer research is then summarized, and examples of a few key applications are given. Finally, future development perspectives are indicated.
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Affiliation(s)
- David Sarrut
- Université de Lyon; CREATIS; CNRS UMR5220; Inserm U1294; INSA-Lyon; Université Lyon 1, Léon Bérard cancer center, Lyon, France
| | - Nicolas Arbor
- Université de Strasbourg, IPHC, CNRS, UMR7178, F-67037 Strasbourg, France
| | - Thomas Baudier
- Université de Lyon; CREATIS; CNRS UMR5220; Inserm U1294; INSA-Lyon; Université Lyon 1, Léon Bérard cancer center, Lyon, France
| | - Damian Borys
- Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland
| | - Ane Etxebeste
- Université de Lyon; CREATIS; CNRS UMR5220; Inserm U1294; INSA-Lyon; Université Lyon 1, Léon Bérard cancer center, Lyon, France
| | - Hermann Fuchs
- MedAustron Ion Therapy Center, Wiener Neustadt, Austria
- Medical University of Vienna, Department of Radiation Oncology, Vienna, Vienna, Währinger Gürtel 18-20, A-1090 Wien, Austria
| | - Jan Gajewski
- Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland
| | | | - Sébastien Jan
- Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), F-91401 Orsay, France
| | - George C Kagadis
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Patras, Greece
| | - Han Gyu Kang
- National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
| | - Assen Kirov
- Memorial Sloan Kettering Cancer, New York, NY 10021, United States of America
| | - Olga Kochebina
- Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), F-91401 Orsay, France
| | - Wojciech Krzemien
- High Energy Physics Division, National Centre for Nuclear Research, Otwock-Świerk, Poland
- Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, S. Lojasiewicza 11, 30-348 Krakow, Poland
- Centre for Theranostics, Jagiellonian University, Kopernika 40 St, 31 501 Krakow, Poland
| | - Antony Lomax
- Center for Proton Therapy, PSI, Switzerland
- Department of Physics, ETH Zurich, Switzerland
| | | | - Christian Pommranz
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Roentgenweg 13, D-72076 Tuebingen, Germany
- Institute for Astronomy and Astrophysics, Eberhard Karls University Tuebingen, Sand 1, D-72076 Tuebingen, Germany
| | - Emilie Roncali
- University of California Davis, Departments of Biomedical Engineering and Radiology, Davis, CA 95616, United States of America
| | - Antoni Rucinski
- Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland
| | - Carla Winterhalter
- Center for Proton Therapy, PSI, Switzerland
- Department of Physics, ETH Zurich, Switzerland
| | - Lydia Maigne
- Université Clermont Auvergne, Laboratoire de Physique de Clermont, CNRS, UMR 6533, F-63178 Aubière, France
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21
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Bianfei S, Fang L, Zhongzheng X, Yuanyuan Z, Tian Y, Tao H, Jiachun M, Xiran W, Siting Y, Lei L. Application of Cherenkov radiation in tumor imaging and treatment. Future Oncol 2022; 18:3101-3118. [PMID: 36065976 DOI: 10.2217/fon-2022-0022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Cherenkov radiation (CR) is the characteristic blue glow that is generated during radiotherapy or radioisotope decay. Its distribution and intensity naturally reflect the actual dose and field of radiotherapy and the location of radioisotope imaging agents in vivo. Therefore, CR can represent a potential in situ light source for radiotherapy monitoring and radioisotope-based tumor imaging. When used in combination with new imaging techniques, molecular probes or nanomedicine, CR imaging exhibits unique advantages (accuracy, low cost, convenience and fast) in tumor radiotherapy monitoring and imaging. Furthermore, photosensitive nanomaterials can be used for CR photodynamic therapy, providing new approaches for integrating tumor imaging and treatment. Here the authors review the latest developments in the use of CR in tumor research and discuss current challenges and new directions for future studies.
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Affiliation(s)
- Shao Bianfei
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Liu Fang
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China.,Department of Radiation Oncology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Xiang Zhongzheng
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Zeng Yuanyuan
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Yang Tian
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - He Tao
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Ma Jiachun
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Wang Xiran
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Yu Siting
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Liu Lei
- Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, China
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22
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Malone CD, Egbulefu C, Zheleznyak A, Polina J, Karmakar P, Black K, Shokeen M, Achilefu S. Activation of nano-photosensitizers by Y-90 microspheres to enhance oxidative stress and cell death in hepatocellular carcinoma. Sci Rep 2022; 12:12748. [PMID: 35882949 PMCID: PMC9325688 DOI: 10.1038/s41598-022-17185-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 07/21/2022] [Indexed: 12/24/2022] Open
Abstract
While radioembolization with yttrium-90 (Y-90) microspheres is a promising treatment for hepatocellular carcinoma (HCC), lower responses in advanced and high-grade tumors present an urgent need to augment its tumoricidal efficacy. The purpose of this study was to determine whether clinically used Y-90 microspheres activate light-responsive nano-photosensitizers to enhance hepatocellular carcinoma (HCC) cell oxidative stress and cytotoxicity over Y-90 alone in vitro. Singlet oxygen and hydroxyl radical production was enhanced when Y-90 microspheres were in the presence of several nano-photosensitizers compared to either alone in cell-free conditions. Both the SNU-387 and HepG2 human HCC cells demonstrated significantly lower viability when treated with low activity Y-90 microspheres (0.1-0.2 MBq/0.2 mL) and a nano-photosensitizer consisting of both titanium dioxide (TiO2) and titanocene (TC) labelled with transferrin (TiO2-Tf-TC) compared to Y-90 microspheres alone or untreated cells. Cellular oxidative stress and cell death demonstrated a linear dependence on Y-90 at higher activities (up to 0.75 MBq/0.2 mL), but was significantly more accentuated in the presence of increasing TiO2-Tf-TC concentrations in the poorly differentiated SNU-387 HCC cell line (p < 0.0001 and p = 0.0002 respectively) but not the well-differentiated HepG2 cell line. Addition of TiO2-Tf-TC to normal human hepatocyte THLE-2 cells did not increase cellular oxidative stress or cell death in the presence of Y-90. The enhanced tumoricidal activity of nano-photosensitizers with Y-90 microspheres is a potentially promising adjunctive treatment strategy for certain patient subsets. Applications in clinically relevant in vivo HCC models are underway.
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Affiliation(s)
- Christopher D Malone
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Ave., Floor 2, St. Louis, MO, 63110, USA.
| | - Christopher Egbulefu
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Ave., Floor 2, St. Louis, MO, 63110, USA
| | - Alexander Zheleznyak
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Ave., Floor 2, St. Louis, MO, 63110, USA
| | - Jahnavi Polina
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Ave., Floor 2, St. Louis, MO, 63110, USA
| | - Partha Karmakar
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Ave., Floor 2, St. Louis, MO, 63110, USA
| | - Kvar Black
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Ave., Floor 2, St. Louis, MO, 63110, USA
| | - Monica Shokeen
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Ave., Floor 2, St. Louis, MO, 63110, USA
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA
| | - Samuel Achilefu
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4515 McKinley Ave., Floor 2, St. Louis, MO, 63110, USA
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA
- Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA
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23
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Abstract
Malignant tumors rank as a leading cause of death worldwide. Accurate diagnosis and advanced treatment options are crucial to win battle against tumors. In recent years, Cherenkov luminescence (CL) has shown its technical advantages and clinical transformation potential in many important fields, particularly in tumor diagnosis and treatment, such as tumor detection in vivo, surgical navigation, radiotherapy, photodynamic therapy, and the evaluation of therapeutic effect. In this review, we summarize the advances in CL for tumor diagnosis and treatment. We first describe the physical principles of CL and discuss the imaging techniques used in tumor diagnosis, including CL imaging, CL endoscope, and CL tomography. Then we present a broad overview of the current status of surgical resection, radiotherapy, photodynamic therapy, and tumor microenvironment monitoring using CL. Finally, we shed light on the challenges and possible solutions for tumor diagnosis and therapy using CL.
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24
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Pratt EC, Skubal M, Mc Larney B, Causa-Andrieu P, Das S, Sawan P, Araji A, Riedl C, Vyas K, Tuch D, Grimm J. Prospective testing of clinical Cerenkov luminescence imaging against standard-of-care nuclear imaging for tumour location. Nat Biomed Eng 2022; 6:559-568. [PMID: 35411113 PMCID: PMC9149092 DOI: 10.1038/s41551-022-00876-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 03/01/2022] [Indexed: 12/16/2022]
Abstract
In oncology, the feasibility of Cerenkov luminescence imaging (CLI) has been assessed by imaging superficial lymph nodes in a few patients undergoing diagnostic 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). However, the weak luminescence signal requires the removal of ambient light. Here we report the development of a clinical CLI fiberscope with a lightproof enclosure, and the clinical testing of the setup using five different radiotracers. In an observational prospective trial (ClinicalTrials.gov identifier NCT03484884 ) involving 96 patients with existing or suspected tumours, scheduled for routine clinical FDG PET or 131I therapy, the level of agreement of CLI with standard-of-care imaging (PET or planar single-photon emission CT) for tumour location was 'acceptable' or higher (≥3 in the 1-5 Likert scale) for 90% of the patients. CLI correlated with the concentration of radioactive activity, and captured therapeutically relevant information from patients undergoing targeted radiotherapy or receiving the alpha emitter 223Ra, which cannot be feasibly imaged clinically. CLI could supplement radiological scans, especially when scanner capacity is limited.
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Affiliation(s)
- Edwin C. Pratt
- Pharmacology Department, Weill Cornell Medical College, New York, NY, 10065, USA.,Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.,Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Magdalena Skubal
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.,Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Benedict Mc Larney
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.,Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Pamela Causa-Andrieu
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Sudeep Das
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.,Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Peter Sawan
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Abdallah Araji
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Christopher Riedl
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Kunal Vyas
- Lightpoint Medical Ltd., Waterside, Chesham, HP5 1PE, UK
| | - David Tuch
- Lightpoint Medical Inc., Cambridge, MA, 02139, USA
| | - Jan Grimm
- Pharmacology Department, Weill Cornell Medical College, New York, NY, USA. .,Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. .,Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. .,Department of Radiology, Weill, Cornell Medical Center, New York, NY, USA.
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25
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Dubal J, Arce P, South C, Florescu L. Cherenkov light emission in molecular radiation therapy of the thyroid and its application to dosimetry. BIOMEDICAL OPTICS EXPRESS 2022; 13:2431-2449. [PMID: 35519238 PMCID: PMC9045923 DOI: 10.1364/boe.448139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 03/07/2022] [Accepted: 03/11/2022] [Indexed: 06/14/2023]
Abstract
Numerical experiments based on Monte Carlo simulations and clinical CT data are performed to investigate the spatial and spectral characteristics of Cherenkov light emission and the relationship between Cherenkov light intensity and deposited dose in molecular radiotherapy of hyperthyroidism and papillary thyroid carcinoma. It is found that Cherenkov light is emitted mostly in the treatment volume, the spatial distribution of Cherenkov light at the surface of the patient presents high-value regions at locations that depend on the symmetry and location of the treatment volume, and the surface light in the near-infrared spectral region originates from the treatment site. The effect of inter-patient variability in the tissue optical parameters and radioisotope uptake on the linear relationship between the dose absorbed by the treatment volume and Cherenkov light intensity at the surface of the patient is investigated, and measurements of surface light intensity for which this effect is minimal are identified. The use of Cherenkov light measurements at the patient surface for molecular radiation therapy dosimetry is also addressed.
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Affiliation(s)
- Jigar Dubal
- Centre for Vision, Speech and Signal Processing, University of Surrey, GU2 7XH, United Kingdom
| | - Pedro Arce
- CIEMAT (Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas), 28040 Madrid, Spain
| | - Christopher South
- Department of Medical Physics, Royal Surrey County Hospital NHS Foundation Trust, Guildford GU2 7XX, United Kingdom
| | - Lucia Florescu
- Centre for Vision, Speech and Signal Processing, University of Surrey, GU2 7XH, United Kingdom
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26
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Li Y, Liu H, Huang N, Wang Z, Zhang C. The Measurement of the Surface Dose in Regular and Small Radiation Therapy Fields Using Cherenkov Imaging. Technol Cancer Res Treat 2022; 21:15330338211073432. [PMID: 35119327 PMCID: PMC8819764 DOI: 10.1177/15330338211073432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Purpose: The aim of this study is to measure the output factor (OF)
and profile of surface dose in regular and small radiation therapy fields using
Cherenkov imaging (CI). Methods: A medical linear accelerator
(linac) was employed to generate radiation fields, including regular open photon
field (ROPF), regular wedge photon field (RWPF), regular electron field (REF)
and small photon field (SPF). The photon beams consisted of two filter modes
including flattening filter (FF) and flattening filter free (FFF). All fields
were delivered to a solid water phantom. Cherenkov light was captured using a
charge-coupled device system during phantom irradiation. The OF and profile of
surface dose measured by CI were compared with those determined by film
measurement, ionization chamber measurement and treatment planning system
calculation in order to examine the feasibility of measuring surface dose OF and
profile using CI. Results: The discrepancy between surface dose OF
measured by CI and that determined by other methods is less than 6% in ROPFs
with size less than 10 × 10 cm2, REFs with size less than 10 × 10
cm2, and SPFs except for 1 × 1 cm2 field. In the flat
profile region, the discrepancy between surface dose profile measured by CI and
that determined by other methods is less than 4% in REFs and less than 3% in
ROPFs, RWPFs, and SPFs except for 1 × 1 cm2 field. The discrepancy of the
surface dose profile is in compliance with the recommendation by IAEA TRS 430
reports. The discrepancy between field width measured by CI and that determined
by film measurement is equal to or less than 2 mm, which is within the tolerance
recommend by the guidelines of linac quality assurance in regular open FF photon
fields, SPFs, and REFs with cone size of 10 × 10 cm2 in area.
Conclusion: CI can be used to quantitatively measure the OF and
profile of surface dose. It is feasible to use CI to measure the surface dose
profile and field width in regular open FF photon fields and SPFs except for
1 × 1 cm2 field.
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Affiliation(s)
- Yi Li
- State Key Laboratory of Transient Optics and Photonics, Xi’an
Institute of Optics and Precision Mechanics, Chinese Academy of Sciences, Xi’an
710119, China
- School of Physics, Xi’an Jiaotong University, Xi’an 710049, China
- University of Chinese Academy of Sciences, Beijing 100049,
China
| | - HongJun Liu
- State Key Laboratory of Transient Optics and Photonics, Xi’an
Institute of Optics and Precision Mechanics, Chinese Academy of Sciences, Xi’an
710119, China
- Collaborative Innovation Center of Extreme Optics, Shanxi
University, Taiyuan 030006, China
- Hongjun Liu, PhD, State Key Laboratory of
Transient Optics and Photonics, Xi’an Institute of Optics and Precision
Mechanics, Chinese Academy of Sciences, Xi’an 710119, China.
Chunmin Zhang, PhD, School of Physics,
Xi’an Jiaotong University, Xi’an 710049, China.
| | - Nan Huang
- State Key Laboratory of Transient Optics and Photonics, Xi’an
Institute of Optics and Precision Mechanics, Chinese Academy of Sciences, Xi’an
710119, China
| | - Zhaolu Wang
- State Key Laboratory of Transient Optics and Photonics, Xi’an
Institute of Optics and Precision Mechanics, Chinese Academy of Sciences, Xi’an
710119, China
| | - Chunmin Zhang
- School of Physics, Xi’an Jiaotong University, Xi’an 710049, China
- Hongjun Liu, PhD, State Key Laboratory of
Transient Optics and Photonics, Xi’an Institute of Optics and Precision
Mechanics, Chinese Academy of Sciences, Xi’an 710119, China.
Chunmin Zhang, PhD, School of Physics,
Xi’an Jiaotong University, Xi’an 710049, China.
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27
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Guo H, Yu J, He X, Yi H, Hou Y, He X. Total Variation Constrained Graph Manifold Learning Strategy for Cerenkov Luminescence Tomography. OPTICS EXPRESS 2022; 30:1422-1441. [PMID: 35209303 DOI: 10.1364/oe.448250] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 12/19/2021] [Indexed: 06/14/2023]
Abstract
Harnessing the power and flexibility of radiolabeled molecules, Cerenkov luminescence tomography (CLT) provides a novel technique for non-invasive visualisation and quantification of viable tumour cells in a living organism. However, owing to the photon scattering effect and the ill-posed inverse problem, CLT still suffers from insufficient spatial resolution and shape recovery in various preclinical applications. In this study, we proposed a total variation constrained graph manifold learning (TV-GML) strategy for achieving accurate spatial location, dual-source resolution, and tumour morphology. TV-GML integrates the isotropic total variation term and dynamic graph Laplacian constraint to make a trade-off between edge preservation and piecewise smooth region reconstruction. Meanwhile, the tetrahedral mesh-Cartesian grid pair method based on the k-nearest neighbour, and the adaptive and composite Barzilai-Borwein method, were proposed to ensure global super linear convergence of the solution of TV-GML. The comparison results of both simulation experiments and in vivo experiments further indicated that TV-GML achieved superior reconstruction performance in terms of location accuracy, dual-source resolution, shape recovery capability, robustness, and in vivo practicability. Significance: We believe that this novel method will be beneficial to the application of CLT for quantitative analysis and morphological observation of various preclinical applications and facilitate the development of the theory of solving inverse problem.
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28
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Chen X, Wang X, Yan T, Zheng Y, Cao H, Ren F, Cao X, Meng X, Lu X, Liang S, Wu K. Sensitivity improved Cerenkov luminescence endoscopy using optimal system parameters. Quant Imaging Med Surg 2022; 12:425-438. [PMID: 34993091 DOI: 10.21037/qims-21-373] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Accepted: 07/06/2021] [Indexed: 12/24/2022]
Abstract
Background The challenges of clinical translation of optical imaging, including the limited availability of clinically used imaging probes and the restricted penetration depth of light propagation in tissues can be avoided using Cerenkov luminescence endoscopy (CLE). However, the clinical applications of CLE are limited due to the low signal level of Cerenkov luminescence and the large transmission loss caused by the endoscope, which results in a relatively low detection sensitivity of current CLE. The aim of this study was to enhance the detection sensitivity of the CLE system and thus improve the system for clinical application in the detection of gastrointestinal diseases. Methods Four optical fiber endoscopes were customized with different system parameters, including monofilament (MF) diameter of imaging fiber bundles, fiber material, probe coating, etc. The endoscopes were connected to the detector via a specifically designed straight connection device to form the CLE system. The β-2-[18F]-Fluoro-2-deoxy-D-glucose (18F-FDG) solution and the radionuclide of Gallium-68 (68Ga) were used to evaluate the performance of the CLE system. The images of the 18F-FDG solution acquired by the CLE were used to optimize imaging parameters of the system. By using the endoscope with optimized parameters, including the MF diameter of imaging fiber bundles, fiber materials, etc., the resolution and sensitivity of the assembled CLE system were measured by imaging the radionuclide of 68Ga. Results The results of 18F-FDG experiments showed that larger MF diameter led to higher collection efficiency. The fiber material and probe coating with high transmission ratios in the range of 400-900 nm also increased signal collection and transmission efficiency. The results of 68Ga evaluations showed that a minimum radioactive activity of radionuclides as low as 0.03 µCi was detected in vitro within 5 minutes, while that of 0.68 µCi can be detected within 1 minute. In vivo experiments also demonstrated that the developed CLE system achieved a high sensitivity at a submicrocurie level; that is, 0.44 µCi within 5 minutes, and 0.83 µCi within 1 minute. The weaker in vivo sensitivity was due to the attenuation of the signal by the mouse tissue skin and the autofluorescence interference produced by biological tissues. Conclusions By optimizing the structural parameters of fiber endoscope and imaging parameters for data acquisition, we developed a CLE system with a sensitivity at submicrocurie level. These results support the possibility that this technology can clinically detect early tumors within 1 minute.
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Affiliation(s)
- Xueli Chen
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of China, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Xinyu Wang
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of China, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Tianyu Yan
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of China, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Yun Zheng
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of China, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Honghao Cao
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of China, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Feng Ren
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of China, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Xu Cao
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of China, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Xiangfeng Meng
- Institute of Medical Device Control, National Institutes for Food and Drug Control, Beijing, China
| | - Xiaojian Lu
- Nanjing Chunhui Science and Technology Industrial Co. Ltd., Nanjing, China
| | - Shuhui Liang
- Fourth Military Medical University, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xi'an, China
| | - Kaichun Wu
- Fourth Military Medical University, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xi'an, China
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29
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Heuvel JO, de Wit-van der Veen BJ, van der Poel HG, van Leeuwen PJ, Bekers EM, Grootendorst MR, Vyas KN, Slump CH, Stokkel MPM. Cerenkov Luminescence Imaging in Prostate Cancer: Not the Only Light That Shines. J Nucl Med 2022; 63:29-35. [PMID: 33931467 PMCID: PMC8717187 DOI: 10.2967/jnumed.120.260034] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 04/01/2021] [Indexed: 12/19/2022] Open
Abstract
Cerenkov luminescence imaging (CLI) is a novel imaging technology that might have the ability to assess surgical margins intraoperatively during prostatectomy using 68Ga-prostate-specific membrane antigen (68Ga-PSMA-11). This study evaluated the accuracy of CLI compared with histopathology and, as an exploratory objective, investigated the characteristics of the identified chemiluminescence signal. Methods: After intravenous injection of a mean 68Ga-PSMA-11 activity of 69 MBq intraoperatively, all excised specimens were imaged with CLI. Areas of increased signal were marked for histopathologic comparison and scored for the likelihood of being a positive surgical margin (PSM) using a 5-point Likert scale. In addition, the chemiluminescence signal was investigated in 3 radioactive and 3 nonradioactive specimens using CLI. Results: In 15 patients, the agreement between CLI and histopathology was 60%; this improved to 83% when including close surgical margins (≤1 mm). In 6 hot spots, CLI correctly identified PSMs on histopathology, located at the apex and mid prostate. In all 15 patients, an increased signal at the prostate base was observed, without the presence of the primary tumor in this area in 8 patients. This chemiluminescence signal was also observed in nonradioactive prostate specimens, with a half-life of 48 ± 11 min. The chemiluminescence hampered the visual interpretation of 4 PSMs at the base. Conclusion: CLI was able to correctly identify margin status, including close margins, in 83% of the cases. The presence of a diathermy-induced chemiluminescent signal hampered image interpretation, especially at the base of the prostate. In the current form, CLI is most applicable to detect PSMs and close margins in the apex and mid prostate.
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Affiliation(s)
- Judith Olde Heuvel
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Technical Medical Centre, University of Twente, Enschede, The Netherlands
| | | | - Henk G van der Poel
- Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Pim J van Leeuwen
- Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Elise M Bekers
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; and
| | | | - Kunal N Vyas
- Lightpoint Medical Ltd., Chesham, United Kingdom
| | - Cornelis H Slump
- Technical Medical Centre, University of Twente, Enschede, The Netherlands
| | - Marcel P M Stokkel
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
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30
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Li J, Dai S, Qin R, Shi C, Ming J, Zeng X, Wen X, Zhuang R, Chen X, Guo Z, Zhang X. Ligand Engineering of Titanium-Oxo Nanoclusters for Cerenkov Radiation-Reinforced Photo/Chemodynamic Tumor Therapy. ACS APPLIED MATERIALS & INTERFACES 2021; 13:54727-54738. [PMID: 34766763 DOI: 10.1021/acsami.1c16213] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
The therapeutic effect of general photodynamic therapy (PDT) is gravely limited by the poor penetration depth of exogenous light radiation. In recent years, Cerenkov radiation (CR) has been exploringly applied to overcome this critical defect. However, the currently reported type I photosensitizers for CR-induced PDT (CRIT) are only TiO2 nanoparticle-based agents with numerous fatally intrinsic drawbacks. Herein, we developed NH2-Ti32O16 nanocluster (NTOC)-derived ultrasmall nanophotosensitizers (NPSs, denoted as TDPs) via innovate ligand engineering. The introduced dopamine (DA) ligands not only facilitate the water solubility and photocatalytic properties of NPSs but also involve the tumor-targeting behavior through the binding affinity with DA receptors on cancer cells. Under CR irradiation, TDPs enable efficient hydroxyl radical (·OH) generation benefiting from the enhanced separation of hole (h+)-electron (e-) pairs, where the h+ will react with H2O to execute type I PDT and the transferred e- can realize the augmentation of Ti3+ to substantially promote the therapeutic index of chemodynamic therapy. This study provides an easy but feasible strategy for constructing versatile NPSs with an ultrasmall framework structure, propounding a refreshing paradigm for implementing efficient CR-induced combined therapy (CRICT) and spurring the development of CR and titanium-familial nanoplatforms in the fields of photocatalysis and nanocatalytic medicine.
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Affiliation(s)
- Jingchao Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Shuqi Dai
- South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou 510640, People's Republic of China
| | - Ruixue Qin
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Changrong Shi
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Jiang Ming
- Department of Chemistry, Fudan University, Shanghai 200438, People's Republic of China
| | - Xinying Zeng
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xuejun Wen
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Rongqiang Zhuang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xiaoyuan Chen
- Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore 117597, Singapore
| | - Zhide Guo
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xianzhong Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
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Abstract
As surgical cases become more complex, intraoperative imaging is increasingly being used. This article discusses emerging imaging technologies used in prostate, kidney, and bladder cancer surgery, including ultrasound, fluorescence-based, and enhanced endoscopy techniques including their strengths and limitations.
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32
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Wei X, Guo H, Yu J, He X, Yi H, Hou Y, He X. A Multilevel Probabilistic Cerenkov Luminescence Tomography Reconstruction Framework Based on Energy Distribution Density Region Scaling. Front Oncol 2021; 11:751055. [PMID: 34745977 PMCID: PMC8570774 DOI: 10.3389/fonc.2021.751055] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 10/05/2021] [Indexed: 11/13/2022] Open
Abstract
Cerenkov luminescence tomography (CLT) is a promising non-invasive optical imaging method with three-dimensional semiquantitative in vivo imaging capability. However, CLT itself relies on Cerenkov radiation, a low-intensity radiation, making CLT reconstruction more challenging than other imaging modalities. In order to solve the ill-posed inverse problem of CLT imaging, some numerical optimization or regularization methods need to be applied. However, in commonly used methods for solving inverse problems, parameter selection significantly influences the results. Therefore, this paper proposed a probabilistic energy distribution density region scaling (P-EDDRS) framework. In this framework, multiple reconstruction iterations are performed, and the Cerenkov source distribution of each reconstruction is treated as random variables. According to the spatial energy distribution density, the new region of interest (ROI) is solved. The size of the region required for the next operation was determined dynamically by combining the intensity characteristics. In addition, each reconstruction source distribution is given a probability weight value, and the prior probability in the subsequent reconstruction is refreshed. Last, all the reconstruction source distributions are weighted with the corresponding probability weights to get the final Cerenkov source distribution. To evaluate the performance of the P-EDDRS framework in CLT, this article performed numerical simulation, in vivo pseudotumor model mouse experiment, and breast cancer mouse experiment. Experimental results show that this reconstruction framework has better positioning accuracy and shape recovery ability and can optimize the reconstruction effect of multiple algorithms on CLT.
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Affiliation(s)
- Xiao Wei
- School of Information and Technology, Northwest University, Xi'an, China.,Xi'an Key Laboratory of Radiomics and Intelligent Perception, Northwest University, Xi'an, China
| | - Hongbo Guo
- School of Information and Technology, Northwest University, Xi'an, China.,Xi'an Key Laboratory of Radiomics and Intelligent Perception, Northwest University, Xi'an, China
| | - Jingjing Yu
- School of Physics and Information Technology, Shaanxi Normal University, Xi'an, China
| | - Xuelei He
- School of Information and Technology, Northwest University, Xi'an, China.,Xi'an Key Laboratory of Radiomics and Intelligent Perception, Northwest University, Xi'an, China
| | - Huangjian Yi
- School of Information and Technology, Northwest University, Xi'an, China.,Xi'an Key Laboratory of Radiomics and Intelligent Perception, Northwest University, Xi'an, China
| | - Yuqing Hou
- School of Information and Technology, Northwest University, Xi'an, China.,Xi'an Key Laboratory of Radiomics and Intelligent Perception, Northwest University, Xi'an, China
| | - Xiaowei He
- School of Information and Technology, Northwest University, Xi'an, China.,Xi'an Key Laboratory of Radiomics and Intelligent Perception, Northwest University, Xi'an, China
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33
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Wang L, He X, Yu J. Prior Compensation Algorithm for Cerenkov Luminescence Tomography From Single-View Measurements. Front Oncol 2021; 11:749889. [PMID: 34631587 PMCID: PMC8495210 DOI: 10.3389/fonc.2021.749889] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 09/06/2021] [Indexed: 11/13/2022] Open
Abstract
Cerenkov luminescence tomography (CLT) has attracted much attention because of the wide clinically-used probes and three-dimensional (3D) quantification ability. However, due to the serious morbidity of 3D optical imaging, the reconstructed images of CLT are not appreciable, especially when single-view measurements are used. Single-view CLT improves the efficiency of data acquisition. It is much consistent with the actual imaging environment of using commercial imaging system, but bringing the problem that the reconstructed results will be closer to the animal surface on the side where the single-view image is collected. To avoid this problem to the greatest extent possible, we proposed a prior compensation algorithm for CLT reconstruction based on depth calibration strategy. This method takes full account of the fact that the attenuation of light in the tissue will depend heavily on the depth of the light source as well as the distance between the light source and the detection plane. Based on this consideration, a depth calibration matrix was designed to calibrate the attenuation between the surface light flux and the density of the internal light source. The feature of the algorithm was that the depth calibration matrix directly acts on the system matrix of CLT reconstruction, rather than modifying the regularization penalty items. The validity and effectiveness of the proposed algorithm were evaluated with a numerical simulation and a mouse-based experiment, whose results illustrated that it located the radiation sources accurately by using single-view measurements.
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Affiliation(s)
- Lin Wang
- School of Information Sciences and Technology, Northwest University, Xi'an, China.,School of Computer Science and Engineering, Xi'an University of Technology, Xi'an, China
| | - Xiaowei He
- School of Information Sciences and Technology, Northwest University, Xi'an, China
| | - Jingjing Yu
- School of Physics and Information Technology, Shaanxi Normal University, Xi'an, China
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34
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Rahman M, Bruza P, Hachadorian R, Alexander D, Cao X, Zhang R, Gladstone DJ, Pogue BW. Optimization of in vivo Cherenkov imaging dosimetry via spectral choices for ambient background lights and filtering. JOURNAL OF BIOMEDICAL OPTICS 2021; 26:JBO-210195RR. [PMID: 34643072 PMCID: PMC8510878 DOI: 10.1117/1.jbo.26.10.106003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/23/2021] [Indexed: 06/13/2023]
Abstract
SIGNIFICANCE The Cherenkov emission spectrum overlaps with that of ambient room light sources. Choice of room lighting devices dramatically affects the efficient detection of Cherenkov emission during patient treatment. AIM To determine optimal room light sources allowing Cherenkov emission imaging in normally lit radiotherapy treatment delivery rooms. APPROACH A variety of commercial light sources and long-pass (LP) filters were surveyed for spectral band separation from the red to near-infrared Cherenkov light emitted by tissue. Their effects on signal-to-noise ratio (SNR), Cherenkov to background signal ratio, and image artifacts were quantified by imaging irradiated tissue equivalent phantoms with an intensified time-gated CMOS camera. RESULTS Because Cherenkov emission from tissue lies largely in the near-infrared spectrum, a controlled choice of ambient light that avoids this spectral band is ideal, along with a camera that is maximally sensitive to it. An RGB LED light source produced the best SNR out of all sources that mimic room light temperature. A 675-nm LP filter on the camera input further reduced ambient light detected (optical density > 3), achieving maximal SNR for Cherenkov emission near 40. Reduction of the room light signal reduced artifacts from specular reflection on the tissue surface and also minimized spurious Cherenkov signals from non-tissue features such as bolus. CONCLUSIONS LP filtering during image acquisition for near-infrared light in tandem with narrow band LED illuminated rooms improves image quality, trading off the loss of red wavelengths for better removal of room light in the image. This spectral filtering is also critically important to remove specular reflection in the images and allow for imaging of Cherenkov emission through clear bolus. Beyond time-gated external beam therapy systems, the spectral separation methods can be utilized for background removal for continuous treatment delivery methods including proton pencil beam scanning systems and brachytherapy.
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Affiliation(s)
- Mahbubur Rahman
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
| | - Petr Bruza
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
| | - Rachael Hachadorian
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
| | - Daniel Alexander
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
| | - Xu Cao
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
| | - Rongxiao Zhang
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
- Dartmouth College, Geisel School of Medicine, Department of Radiation Oncology, Hanover, New Hampshire, United States
- Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, New Hampshire, United States
| | - David J. Gladstone
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
- Dartmouth College, Geisel School of Medicine, Department of Radiation Oncology, Hanover, New Hampshire, United States
- Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, New Hampshire, United States
| | - Brian W. Pogue
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
- Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, New Hampshire, United States
- Dartmouth College, Geisel School of Medicine, Department of Surgery, Hanover, New Hampshire, United States
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35
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Mc Larney B, Skubal M, Grimm J. A review of recent and emerging approaches for the clinical application of Cerenkov luminescence imaging. FRONTIERS IN PHYSICS 2021; 9:684196. [PMID: 36845872 PMCID: PMC9957555 DOI: 10.3389/fphy.2021.684196] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Cerenkov luminescence (CL) is a blue-weighted emission of light produced by a vast array of clinically approved radioisotopes and LINAC accelerators. When β particles (emitted during the decay of radioisotopes) are present in a medium such as water or tissue, they are able to travel faster than the speed of light in that medium and in doing so polarize the molecules around them. Once the particle has left the local area, the polarized molecules relax and return to their baseline state releasing the additional energy as light (luminescence). This blue glow has commonly been used to determine the output of nuclear power plant cores and, in recent years, has found traction in the preclinical and clinical imaging field. This brief review will discuss the technology which has enabled the emergence of the biomedical Cerenkov imaging field, recent pre-clinical studies with potential clinical translation of Cerenkov luminescence imaging (CLI) and the current clinical implementations of the method. Finally, an outlook is given as to the direction in which the field is heading.
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Affiliation(s)
- Benedict Mc Larney
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Magdalena Skubal
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jan Grimm
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA
- Department of Radiology, Weill Cornell Medical College, New York, NY, USA
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36
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Shi X, Cao C, Zhang Z, Tian J, Hu Z. Radiopharmaceutical and Eu 3+ doped gadolinium oxide nanoparticles mediated triple-excited fluorescence imaging and image-guided surgery. J Nanobiotechnology 2021; 19:212. [PMID: 34271928 PMCID: PMC8283963 DOI: 10.1186/s12951-021-00920-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 05/31/2021] [Indexed: 11/11/2022] Open
Abstract
Cerenkov luminescence imaging (CLI) is a novel optical imaging technique that has been applied in clinic using various radionuclides and radiopharmaceuticals. However, clinical application of CLI has been limited by weak optical signal and restricted tissue penetration depth. Various fluorescent probes have been combined with radiopharmaceuticals for improved imaging performances. However, as most of these probes only interact with Cerenkov luminescence (CL), the low photon fluence of CL greatly restricted it's interaction with fluorescent probes for in vivo imaging. Therefore, it is important to develop probes that can effectively convert energy beyond CL such as β and γ to the low energy optical signals. In this study, a Eu3+ doped gadolinium oxide (Gd2O3:Eu) was synthesized and combined with radiopharmaceuticals to achieve a red-shifted optical spectrum with less tissue scattering and enhanced optical signal intensity in this study. The interaction between Gd2O3:Eu and radiopharmaceutical were investigated using 18F-fluorodeoxyglucose (18F-FDG). The ex vivo optical signal intensity of the mixture of Gd2O3:Eu and 18F-FDG reached 369 times as high as that of CLI using 18F-FDG alone. To achieve improved biocompatibility, the Gd2O3:Eu nanoparticles were then modified with polyvinyl alcohol (PVA), and the resulted nanoprobe PVA modified Gd2O3:Eu (Gd2O3:Eu@PVA) was applied in intraoperative tumor imaging. Compared with 18F-FDG alone, intraoperative administration of Gd2O3:Eu@PVA and 18F-FDG combination achieved a much higher tumor-to-normal tissue ratio (TNR, 10.24 ± 2.24 vs. 1.87 ± 0.73, P = 0.0030). The use of Gd2O3:Eu@PVA and 18F-FDG also assisted intraoperative detection of tumors that were omitted by preoperative positron emission tomography (PET) imaging. Further experiment of image-guided surgery demonstrated feasibility of image-guided tumor resection using Gd2O3:Eu@PVA and 18F-FDG. In summary, Gd2O3:Eu can achieve significantly optimized imaging property when combined with 18F-FDG in intraoperative tumor imaging and image-guided tumor resection surgery. It is expected that the development of the Gd2O3:Eu nanoparticle will promote investigation and application of novel nanoparticles that can interact with radiopharmaceuticals for improved imaging properties. This work highlighted the impact of the nanoprobe that can be excited by radiopharmaceuticals emitting CL, β, and γ radiation for precisely imaging of tumor and intraoperatively guide tumor resection.
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Affiliation(s)
- Xiaojing Shi
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China
- School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China
| | - Caiguang Cao
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China
- School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China
| | - Zeyu Zhang
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine, Beihang University, Beijing, China
| | - Jie Tian
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China
- School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine, Beihang University, Beijing, China
| | - Zhenhua Hu
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China
- School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China
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37
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Algorri JF, Ochoa M, Roldán-Varona P, Rodríguez-Cobo L, López-Higuera JM. Light Technology for Efficient and Effective Photodynamic Therapy: A Critical Review. Cancers (Basel) 2021; 13:3484. [PMID: 34298707 PMCID: PMC8307713 DOI: 10.3390/cancers13143484] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/17/2021] [Accepted: 07/07/2021] [Indexed: 12/18/2022] Open
Abstract
Photodynamic therapy (PDT) is a cancer treatment with strong potential over well-established standard therapies in certain cases. Non-ionising radiation, localisation, possible repeated treatments, and stimulation of immunological response are some of the main beneficial features of PDT. Despite the great potential, its application remains challenging. Limited light penetration depth, non-ideal photosensitisers, complex dosimetry, and complicated implementations in the clinic are some limiting factors hindering the extended use of PDT. To surpass actual technological paradigms, radically new sources, light-based devices, advanced photosensitisers, measurement devices, and innovative application strategies are under extensive investigation. The main aim of this review is to highlight the advantages/pitfalls, technical challenges and opportunities of PDT, with a focus on technologies for light activation of photosensitisers, such as light sources, delivery devices, and systems. In this vein, a broad overview of the current status of superficial, interstitial, and deep PDT modalities-and a critical review of light sources and their effects on the PDT process-are presented. Insight into the technical advancements and remaining challenges of optical sources and light devices is provided from a physical and bioengineering perspective.
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Affiliation(s)
- José Francisco Algorri
- Photonics Engineering Group, University of Cantabria, 39005 Santander, Spain; (M.O.); (P.R.-V.); (J.M.L.-H.)
- Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain
| | - Mario Ochoa
- Photonics Engineering Group, University of Cantabria, 39005 Santander, Spain; (M.O.); (P.R.-V.); (J.M.L.-H.)
- Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain
| | - Pablo Roldán-Varona
- Photonics Engineering Group, University of Cantabria, 39005 Santander, Spain; (M.O.); (P.R.-V.); (J.M.L.-H.)
- Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain
- CIBER-bbn, Institute of Health Carlos III, 28029 Madrid, Spain;
| | | | - José Miguel López-Higuera
- Photonics Engineering Group, University of Cantabria, 39005 Santander, Spain; (M.O.); (P.R.-V.); (J.M.L.-H.)
- Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain
- CIBER-bbn, Institute of Health Carlos III, 28029 Madrid, Spain;
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38
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Concilio SC, Russell SJ, Peng KW. A brief review of reporter gene imaging in oncolytic virotherapy and gene therapy. Mol Ther Oncolytics 2021; 21:98-109. [PMID: 33981826 PMCID: PMC8065251 DOI: 10.1016/j.omto.2021.03.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Reporter gene imaging (RGI) can accelerate development timelines for gene and viral therapies by facilitating rapid and noninvasive in vivo studies to determine the biodistribution, magnitude, and durability of viral gene expression and/or virus infection. Functional molecular imaging systems used for this purpose can be divided broadly into deep-tissue and optical modalities. Deep-tissue modalities, which can be used in animals of any size as well as in human subjects, encompass single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional/molecular magnetic resonance imaging (f/mMRI). Optical modalities encompass fluorescence, bioluminescence, Cerenkov luminescence, and photoacoustic imaging and are suitable only for small animal imaging. Here we discuss the mechanisms of action and relative merits of currently available reporter gene systems, highlighting the strengths and weaknesses of deep tissue versus optical imaging systems and the hardware/reagents that are used for data capture and processing. In light of recent technological advances, falling costs of imaging instruments, better availability of novel radioactive and optical tracers, and a growing realization that RGI can give invaluable insights across the entire in vivo translational spectrum, the approach is becoming increasingly essential to facilitate the competitive development of new virus- and gene-based drugs.
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Affiliation(s)
| | | | - Kah-Whye Peng
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA
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39
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Berrens AC, van Leeuwen PJ, Maurer T, Hadaschik BA, Krafft U. Implementation of radioguided surgery in prostate cancer. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF RADIOPHARMACEUTICAL CHEMISTRY AND BIOLOGY 2021; 65:202-214. [PMID: 34105337 DOI: 10.23736/s1824-4785.21.03348-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
With the development of new imaging technologies and tracers, the applications of radioguided surgery for prostate cancer are growing rapidly. The current paper aims to give an overview of the recent advances of radioguided surgery in the management of prostate cancer. We performed a literature search to give an overview of the current status of radioguided surgery for prostate cancer. Three modalities of radioguided surgery, the sentinel node procedure, Cerenkov Luminescence / beta-radio-guided surgery and radio-guided salvage surgery in recurrent prostate cancer, were reviewed in detail. Radioguided surgery for prostate cancer has shown promising value in the treatment of primary diagnosed prostate cancer and recurrent loco-regional lymph node positive prostate cancer. Advances have been made into minimal invasive (robot-assisted) laparoscopic surgery. The sentinel node procedure for prostate cancer has been further developed and is currently performed with high diagnostic sensitivity. Cerenkov luminescence imaging is a feasible and encouraging technique for intraoperative margin assessment in prostate cancer. Radioguided surgery in recurrent prostate cancer has shown to be feasible, yielding high sensitivity and specificity for detecting small local recurrences and metastases. With the availability of different new tracers, the road has been paved towards clinically feasible radioguided surgery for prostate cancer. Novel technologies now being developed for minimal invasive surgery are speeding up clinical research. Currently, none of the radioguided surgery techniques mentioned have been accepted as standard of care.
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Affiliation(s)
- Anne-Claire Berrens
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Pim J van Leeuwen
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Tobias Maurer
- Department of Urology, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Boris A Hadaschik
- Department of Urology, West German Cancer Center, Essen University Hospital, Essen, Germany
| | - Ulrich Krafft
- Department of Urology, West German Cancer Center, Essen University Hospital, Essen, Germany -
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40
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Zhang Q, Pratt EC, Tamura R, Ogirala A, Hsu C, Farahmand N, O’Brien S, Grimm J. Ultrasmall Downconverting Nanoparticle for Enhanced Cerenkov Imaging. NANO LETTERS 2021; 21:4217-4224. [PMID: 33950695 PMCID: PMC8879088 DOI: 10.1021/acs.nanolett.1c00049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Cerenkov imaging provides an opportunity to expand the application of approved radiotracers and therapeutic agents by utilizing them for optical approaches, which opens new avenues for nuclear imaging. The dominating Cerenkov radiation is in the UV/blue region, where it is readily absorbed by human tissue, reducing its utility in vivo. To solve this problem, we propose a strategy to shift Cerenkov light to the more penetrative red-light region through the use of a fluorescent down-conversion technique, based upon europium oxide nanoparticles. We synthesized square-shape ultrasmall Eu2O3 nanoparticles, functionalized with polyethylene glycol and chelate-free radiolabeled for intravenous injection into mice to visualize the lymph node and tumor. By adding trimethylamine N-oxide during the synthesis, we significantly increased the brightness of the particle and synthesized the (to-date) smallest radiolabeled europium-based nanoparticle. These features allow for the exploration of Eu2O3 nanoparticles as a preclinical cancer diagnosis platform with multimodal imaging capability.
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Affiliation(s)
- Qize Zhang
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Department of Chemistry and Biochemistry, The City College of New York, 1024 Marshak, 160 Convent Avenue, New York, New York 10031, USA
- Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York 10016, USA
| | - Edwin C. Pratt
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Department of Pharmacology, Weill Cornell Medical College, New York, NY 10021, USA
| | - Ryo Tamura
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Anuja Ogirala
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Charlene Hsu
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Nasim Farahmand
- Department of Chemistry and Biochemistry, The City College of New York, 1024 Marshak, 160 Convent Avenue, New York, New York 10031, USA
- Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York 10016, USA
| | - Stephen O’Brien
- Department of Chemistry and Biochemistry, The City College of New York, 1024 Marshak, 160 Convent Avenue, New York, New York 10031, USA
- Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York 10016, USA
| | - Jan Grimm
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Department of Pharmacology, Weill Cornell Medical College, New York, NY 10021, USA
- Department of Radiology, Weill Cornell Medical College, New York, NY 10021, USA
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41
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Collamati F, van Oosterom MN, Hadaschik BA, Fragoso Costa P, Darr C. Beta radioguided surgery: towards routine implementation? THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2021; 65:229-243. [PMID: 34014062 DOI: 10.23736/s1824-4785.21.03358-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
INTRODUCTION In locally or locally advanced solid tumors, surgery still remains a fundamental treatment method. However, conservative resection is associated with high collateral damage and functional limitations of the patient. Furthermore, the presence of residual tumor tissue following conservative surgical treatment is currently a common cause of locally recurrent cancer or of distant metastases. Reliable intraoperative detection of small cancerous tissue would allow surgeons to selectively resect malignant areas: this task can be achieved by means of image-guided surgery, such as beta radioguided surgery (RGS). EVIDENCE ACQUISITION In this paper, a comprehensive review of beta RGS is given, starting from the physical principles that differentiate beta from gamma radiation, that has already its place in nuclear medicine current practice. Also, the recent clinical feasibility of using Cerenkov radiation is discussed. EVIDENCE SYNTHESIS Despite being first proposed several decades ago, only in the last years a remarkable interest in beta RGS has been observed, probably driven by the diffusion of PET radio tracers. Today several different approaches are being pursued to assess the effectiveness of such a technique, including both beta+ and beta- emitting radiopharmaceuticals. CONCLUSIONS Beta RGS shows some peculiarities that can present it as a very promising complementary technique to standard procedures. Good results are being obtained in several tests, both ex vivo and in vivo. This might however be the time to initiate the trials to demonstrate the real clinical value of these technologies with seemingly clear potential.
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Affiliation(s)
| | - Matthias N van Oosterom
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.,Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Boris A Hadaschik
- Department of Urology, University Hospital Essen, Essen, Germany.,German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
| | - Pedro Fragoso Costa
- German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.,Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
| | - Christopher Darr
- Department of Urology, University Hospital Essen, Essen, Germany.,German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
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van Dam RM, Chatziioannou AF. Cerenkov Luminescence Imaging in the Development and Production of Radiopharmaceuticals. FRONTIERS IN PHYSICS 2021; 9:632056. [PMID: 36213527 PMCID: PMC9544387 DOI: 10.3389/fphy.2021.632056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Over the past several years there has been an explosion of interest in exploiting Cerenkov radiation to enable in vivo and intraoperative optical imaging of subjects injected with trace amounts of radiopharmaceuticals. At the same time, Cerenkov luminescence imaging (CLI) also has been serving as a critical tool in radiochemistry, especially for the development of novel microfluidic devices for producing radiopharmaceuticals. By enabling microfluidic processes to be monitored non-destructively in situ, CLI has made it possible to literally watch the activity distribution as the synthesis occurs, and to quantitatively measure activity propagation and losses at each step of synthesis, paving the way for significant strides forward in performance and robustness of those devices. In some cases, CLI has enabled detection and resolution of unexpected problems not observable via standard optical methods. CLI is also being used in analytical radiochemistry to increase the reliability of radio-thin layer chromatography (radio-TLC) assays. Rapid and high-resolution Cerenkov imaging of radio-TLC plates enables detection of issues in the spotting or separation process, improves chromatographic resolution (and/or allows reduced separation distance and time), and enables increased throughput by allowing multiple samples to be spotted side-by-side on a single TLC plate for parallel separation and readout. In combination with new multi-reaction microfluidic chips, this is creating a new possibility for high-throughput optimization in radiochemistry. In this mini review, we provide an overview of the role that CLI has played to date in the radiochemistry side of radiopharmaceuticals.
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Affiliation(s)
- R. Michael van Dam
- UCLA Crump Institute for Molecular Imaging, Los Angeles, CA, United States
- UCLA Department of Molecular and Medical Pharmacology, Los Angeles, CA, United States
| | - Arion F. Chatziioannou
- UCLA Crump Institute for Molecular Imaging, Los Angeles, CA, United States
- UCLA Department of Molecular and Medical Pharmacology, Los Angeles, CA, United States
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Pratt EC, Tamura R, Grimm J. Cerenkov Imaging. Mol Imaging 2021. [DOI: 10.1016/b978-0-12-816386-3.00028-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Li Y, Liu H, Huang N, Wang Z, Zhang C. Using Cherenkov imaging to monitor the match line between photon and electron radiation therapy fields on biological tissue phantoms. JOURNAL OF BIOMEDICAL OPTICS 2020; 25:JBO-200268RR. [PMID: 33300317 PMCID: PMC7725107 DOI: 10.1117/1.jbo.25.12.125001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 11/16/2020] [Indexed: 06/12/2023]
Abstract
SIGNIFICANCE Due to patients' respiratory movement or involuntary body movements during breast cancer radiotherapy, the mismatched adjacent fields in surface exposure regions could result in insufficient dosage or overdose in these regions, which would lead to tissue injury, excessive skin burns, and potential death. Cherenkov luminescence imaging (CLI) could be used to effectively detect the matching information of adjacent radiation fields without extra radiation or invasive imaging. AIM Our objective was to provide a biological experimental basis for monitoring matching of adjacent radiation fields between photon and electron fields due to introduced shifts during radiotherapy by CLI technique. APPROACH A medical accelerator was used to generate photon and electron fields. An industrial camera system was adopted to image the excited CLI signal during irradiation of chicken tissue with yellow (group A and group C experiments) or black color (group B experiment). The following introduced shifts were tested: 10, 5, 2, and 0 mm toward superior or inferior direction. A model was introduced to deal with matching error analysis of adjacent radiation fields due to introduced shifts with adapted plans used to treat neoplasms of the right breast with supraclavicular nodes or internal mammary lymph node. RESULTS The matching values between photon and electron fields were consistent with the tested introduced shifts during yellow chicken irradiation. In group A, average discrepancies were 0.59 ± 0.35 mm and 0.68 ± 0.37 mm for photon fields and electron fields in anterior/posterior (AP) direction, with 87% and 75% of measurement within 1 mm, respectively. In group C, average discrepancies were 0.80 ± 0.65 mm and 1.07 ± 0.57 mm for oblique photon field with gantry angles of 330 deg and 150 deg, with 66% and 65% of measurement within 1 mm, respectively. The average discrepancies were 0.44 ± 0.30 mm for electron field in the AP direction, with 94% of measurement within 1 mm. The matching error introduced by the proposed method was less than 1.5 mm for AP fields and 2 mm for oblique incidence fields. However, the field matching could not be monitored with black chicken tissue irradiation due to a weak CLI signal that could hardly be extracted from background noise in group B. CONCLUSIONS CLI is demonstrated for the quantitative monitoring of the field match line on light biological tissue phantoms and has potential for monitoring of field matching in surface tissue during breast cancer radiotherapy.
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Affiliation(s)
- Yi Li
- Chinese Academy of Sciences, Xi’an Institute of Optics and Precision Mechanics, State Key Laboratory of Transient Optics and Photonics, Xi’an, China
- Xi’an Jiaotong University, School of Physics, Xi’an, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Hongjun Liu
- Chinese Academy of Sciences, Xi’an Institute of Optics and Precision Mechanics, State Key Laboratory of Transient Optics and Photonics, Xi’an, China
- Shanxi University, Collaborative Innovation Center of Extreme Optics, Taiyuan, China
| | - Nan Huang
- Chinese Academy of Sciences, Xi’an Institute of Optics and Precision Mechanics, State Key Laboratory of Transient Optics and Photonics, Xi’an, China
| | - Zhaolu Wang
- Chinese Academy of Sciences, Xi’an Institute of Optics and Precision Mechanics, State Key Laboratory of Transient Optics and Photonics, Xi’an, China
| | - Chunmin Zhang
- Xi’an Jiaotong University, School of Physics, Xi’an, China
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Dang Q, Jiang Y, Wang J, Wang J, Zhang Q, Zhang M, Luo S, Xie Y, Pu K, Li Q, Li Z. Room-Temperature Phosphorescence Resonance Energy Transfer for Construction of Near-Infrared Afterglow Imaging Agents. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2020; 32:e2006752. [PMID: 33175432 DOI: 10.1002/adma.202006752] [Citation(s) in RCA: 165] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 10/22/2020] [Indexed: 06/11/2023]
Abstract
Afterglow imaging that detects photons after cessation of optical excitation avoids tissue autofluorescence and thus possesses higher sensitivity than traditional fluorescence imaging. Purely organic molecules with room-temperature phosphorescence (RTP) have emerged as a new library of benign afterglow agents. However, most RTP luminogens only emit visible light with shallow tissue penetration, constraining their in vivo applications. This study presents an organic RTP nanoprobe (mTPA-N) with emission in the NIR range for in vivo afterglow imaging. Such a probe is composed of RTP molecule (mTPA) as the phosphorescent generator and an NIR-fluorescent dye as the energy acceptor to enable room-temperature phosphorescence resonance energy transfer (RT-PRET), ultimately resulting in redshifted phosphorescent emission at 780 nm. Because of the elimination of background noise and redshifted afterglow luminescence in a biologically transparent window, mTPA-N permits imaging of lymph nodes in living mice with a high signal-to-noise ratio. This study thus opens up a universal approach to develop organic RTP luminogens into NIR afterglow imaging agents via construction of RT-PRET.
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Affiliation(s)
- Qianxi Dang
- Sauvage Center for Molecular Sciences, Department of Chemistry, Wuhan University, Wuhan, 430072, China
| | - Yuyan Jiang
- School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637457, Singapore
| | - Jinfeng Wang
- Sauvage Center for Molecular Sciences, Department of Chemistry, Wuhan University, Wuhan, 430072, China
| | - Jiaqiang Wang
- Institute of Molecular Aggregation Science, Tianjin University, Tianjin, 300072, China
| | - Qunhua Zhang
- Sauvage Center for Molecular Sciences, Department of Chemistry, Wuhan University, Wuhan, 430072, China
| | - Mingkang Zhang
- Sauvage Center for Molecular Sciences, Department of Chemistry, Wuhan University, Wuhan, 430072, China
| | - Simeng Luo
- Sauvage Center for Molecular Sciences, Department of Chemistry, Wuhan University, Wuhan, 430072, China
| | - Yujun Xie
- Institute of Molecular Aggregation Science, Tianjin University, Tianjin, 300072, China
| | - Kanyi Pu
- School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637457, Singapore
- Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore
| | - Qianqian Li
- Sauvage Center for Molecular Sciences, Department of Chemistry, Wuhan University, Wuhan, 430072, China
| | - Zhen Li
- Sauvage Center for Molecular Sciences, Department of Chemistry, Wuhan University, Wuhan, 430072, China
- Institute of Molecular Aggregation Science, Tianjin University, Tianjin, 300072, China
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Cao X, Zhang J, Yang J, Fan C, Zhao F, Zhou W, Wang L, Geng G, Zhou M, Chen X. A deep unsupervised clustering-based post-processing framework for high-fidelity Cerenkov luminescence tomography. JOURNAL OF APPLIED PHYSICS 2020; 128. [DOI: 10.1063/5.0025877] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Cerenkov Luminescence Tomography (CLT) is a promising optical molecular imaging technology. It involves the three-dimensional reconstruction of the distribution of radionuclide probes inside a single object to indicate a tumor's localization and distribution. However, reconstruction using CLT suffers from severe ill-posedness, resulting in numerous artifacts within the reconstructed images. These artifacts influence the visual effect and may misguide the medical professional (diagnostician), resulting in a wrong diagnosis. Here, we proposed a deep unsupervised clustering-based post-processing framework to eliminate artifacts and facilitate high-fidelity CLT. First, an initial reconstructed image was obtained by a specific reconstruction method. Second, voxel data were generated based on the initial reconstructed result. Third, these voxels were divided into three groups, and only the group with the highest mean intensity was chosen as the final reconstructed result. A group of numerical simulation and in vivo mouse-based experiments were conducted to assess the presented framework's feasibility and potential. The results indicated that the proposed framework could reduce the number of artifacts effectively. The reconstructed image's shape and distribution were more similar to the actual light source than those obtained without the proposed framework.
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Affiliation(s)
- Xin Cao
- School of Information Sciences and Technology, Northwest University 1 , Xi'an, Shaanxi 710127, China
| | - Jun Zhang
- School of Information Sciences and Technology, Northwest University 1 , Xi'an, Shaanxi 710127, China
| | - Jianan Yang
- School of Information Sciences and Technology, Northwest University 1 , Xi'an, Shaanxi 710127, China
| | - Chunxiao Fan
- School of Computer Science and Information Engineering, Hefei University of Technology 2 , Hefei, Anhui 230601, China
| | - Fengjun Zhao
- School of Information Sciences and Technology, Northwest University 1 , Xi'an, Shaanxi 710127, China
| | - Wei Zhou
- School of Information Sciences and Technology, Northwest University 1 , Xi'an, Shaanxi 710127, China
| | - Lin Wang
- School of Information Sciences and Technology, Northwest University 1 , Xi'an, Shaanxi 710127, China
| | - Guohua Geng
- School of Information Sciences and Technology, Northwest University 1 , Xi'an, Shaanxi 710127, China
| | - Mingquan Zhou
- Engineering Research Center of Virtual Reality and Applications, Ministry of Education, Beijing Key Laboratory of Digital Preservation and Virtual Reality for Cultural Heritage, Beijing Normal University 3 , Beijing, China
| | - Xueli Chen
- Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education & School of Life Science and Technology, Xidian University 4 , Xi'an, Shaanxi 710071, China
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Yamamoto S. Discovery of the luminescence of water during irradiation of radiation at a lower energy than the Cherenkov light threshold. Radiol Phys Technol 2020; 14:16-24. [PMID: 33037579 DOI: 10.1007/s12194-020-00588-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/24/2020] [Accepted: 09/26/2020] [Indexed: 11/29/2022]
Abstract
It is widely believed that light is not emitted in water during irradiation of radiation at energies lower than the Cherenkov light threshold. Contrary to this consensus, we discovered that light (luminescence) is emitted in water during irradiation of radiation, and imaging of this luminescence was possible. In this review, the author describes the optical images obtained for various types of radiation, their characteristics and origins, and potential applications of the luminescence of water during irradiation at a lower energy than the Cherenkov light threshold. The author also describes the luminescence of other transparent materials and future prospects of the discovered luminescence.
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Affiliation(s)
- Seiichi Yamamoto
- Department of Integrated Health Science, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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Cai M, Zhang Z, Shi X, Yang J, Hu Z, Tian J. Non-Negative Iterative Convex Refinement Approach for Accurate and Robust Reconstruction in Cerenkov Luminescence Tomography. IEEE TRANSACTIONS ON MEDICAL IMAGING 2020; 39:3207-3217. [PMID: 32324543 DOI: 10.1109/tmi.2020.2987640] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Cerenkov luminescence tomography (CLT) is a promising imaging tool for obtaining three-dimensional (3D) non-invasive visualization of the in vivo distribution of radiopharmaceuticals. However, the reconstruction performance remains unsatisfactory for biomedical applications because the inverse problem of CLT is severely ill-conditioned and intractable. In this study, therefore, a novel non-negative iterative convex refinement (NNICR) approach was utilized to improve the CLT reconstruction accuracy, robustness as well as the shape recovery capability. The spike and slab prior information was employed to capture the sparsity of Cerenkov source, which could be formalized as a non-convex optimization problem. The NNICR approach solved this non-convex problem by refining the solutions of the convex sub-problems. To evaluate the performance of the NNICR approach, numerical simulations and in vivo tumor-bearing mice models experiments were conducted. Conjugated gradient based Tikhonov regularization approach (CG-Tikhonov), fast iterative shrinkage-thresholding algorithm based Lasso approach (Fista-Lasso) and Elastic-Net regularization approach were used for the comparison of the reconstruction performance. The results of these experiments demonstrated that the NNICR approach obtained superior reconstruction performance in terms of location accuracy, shape recovery capability, robustness and in vivo practicability. It was believed that this study would facilitate the preclinical and clinical applications of CLT in the future.
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Cai P, Yang W, He Z, Jia H, Wang H, Zhao W, Gao L, Zhang Z, Gao F, Gao X. A chlorin-lipid nanovesicle nucleus drug for amplified therapeutic effects of lung cancer by internal radiotherapy combined with the Cerenkov radiation-induced photodynamic therapy. Biomater Sci 2020; 8:4841-4851. [PMID: 32776056 DOI: 10.1039/d0bm00778a] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Traditional photodynamic therapy (PDT) requires external light excitation to produce reactive oxygen species (ROSs) for the treatment of tumors. Due to problems of light penetration, traditional PDT is limited by the location and depth of the tumor. In this study, we rationally designed and constructed a novel strategy to amplify the therapeutic effect of PDT. We prepared a chlorin-lipid nanovesicle based on the conjugates of chlorin e6 (Ce 6) and phospholipids, with the surface conjugating the aptamer for lung cancer targeting, GLT21.T. 131I-labeled bovine serum albumin (131I-BSA) was loaded into the chlorin-lipid nanovesicle cavity (131I-BSA@LCN-Apt). 131I not only plays a role in radiotherapy, but its Cerenkov radiation (CR), as an internal light source, can also stimulate Ce6 to produce ROSs without external light excitation. The in vitro and in vivo therapeutic effects in subcutaneous lung tumor models and orthotopic lung tumor models indicated that 131I-BSA@LCN-Apt produced a powerful anti-tumor effect through synergistic radiotherapy and CR-PDT, which almost caused complete tumor growth regression. After treatment, the survival time of the mice was significantly prolonged. During the treatment, no obvious side effects were found by histopathology of important organs, hematology and biochemistry analysis except the decrease of the white blood cell count (WBC). The study provides a major tool for deep-seated tumors to obtain amplified therapeutic effects by synergistic radiotherapy and CR-PDT without the use of any external light source.
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Affiliation(s)
- Pengju Cai
- CAS Key Laboratory for the Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
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Lioret V, Bellaye PS, Arnould C, Collin B, Decréau RA. Dual Cherenkov Radiation-Induced Near-Infrared Luminescence Imaging and Photodynamic Therapy toward Tumor Resection. J Med Chem 2020; 63:9446-9456. [PMID: 32706253 DOI: 10.1021/acs.jmedchem.0c00625] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Cherenkov radiation (CR), the blue light seen in nuclear reactors, is emitted by some radiopharmaceuticals. This study showed that (1) a portion of CR could be transferred in the region of the optical spectrum, where biological tissues are most transparent: as a result, upon radiance amplification in the near-infrared window, the detection of light could occur twice deeper in tissues than during classical Cherenkov luminescence imaging and (2) Cherenkov-photodynamic therapy (CR-PDT) on cells could be achieved under conditions mimicking unlimited depth using the CR-embarked light source, which is unlike standard PDT, where light penetration depth is limited in biological tissues. Both results are of utmost importance for simultaneous applications in tumor resection and post-resection treatment of remaining unresected margins, thanks to a molecular construct designed to raise its light collection efficiency (i.e., CR energy transfer) by conjugation with multiple CR-absorbing (water-soluble) antenna followed by intramolecular-FRET/TBET energy transfers.
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Affiliation(s)
- Vivian Lioret
- ICMUB Institute (Chemistry Department) Sciences Mirande, Université de Bourgogne Franche Comté, 9 Avenue Alain Savary, Dijon 21078, France
| | | | | | - Bertrand Collin
- Centre George François Leclerc, 1 rue du Professeur Marion, Dijon 21079, France
| | - Richard A Decréau
- ICMUB Institute (Chemistry Department) Sciences Mirande, Université de Bourgogne Franche Comté, 9 Avenue Alain Savary, Dijon 21078, France
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