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Hu X, Wang Z, Zhu Y, Li Z, Yan H, Zhao X, Wang Q. Advancements in molecular imaging for the diagnosis and treatment of pancreatic ductal adenocarcinoma. NANOSCALE ADVANCES 2025:d4na01080a. [PMID: 40270837 PMCID: PMC12012634 DOI: 10.1039/d4na01080a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 04/03/2025] [Indexed: 04/25/2025]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor characterized by poor overall patient survival and prognosis, largely due to challenges in early diagnosis, limited surgical options, and a high propensity for therapy resistance. The integration of various imaging modalities through molecular imaging techniques, particularly multimodal molecular imaging, offers the potential to provide more precise and comprehensive information about the lesion. With advances in nanomedicine, new imaging and drug delivery approaches that allow the development of multifunctional theranostic agents offer opportunities for improving pancreatic cancer treatment using precision oncology. Herein, we review the diagnostic and therapeutic applications of molecular imaging for PDAC and discuss the adoption of multimodal imaging approaches that combine the strengths of different imaging techniques to enhance diagnostic accuracy and therapeutic efficacy. We emphasize the significant role of nanomedicine technology in advancing multimodal molecular imaging and theranostics, and their potential impact on PDAC management. This comprehensive review aims to serve as a valuable reference for researchers and clinicians, offering insights into the current state of molecular imaging in PDAC and outlining future directions for improving early diagnosis, combination therapies, and prognostic evaluations.
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Affiliation(s)
- Xun Hu
- Department of Diagnostic Imaging, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China
| | - Zihua Wang
- School of Basic Medical Sciences, Fujian Medical University Fuzhou 350122 Fujian Province China
| | - Yuting Zhu
- Department of Diagnostic Imaging, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China
| | - Zhangfu Li
- Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital Shenzhen Guangdong 518036 China
| | - Hao Yan
- Tsinghua Shenzhen International Graduate School/Tsinghua University Shenzhen 518055 China
| | - Xinming Zhao
- Department of Diagnostic Imaging, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China
| | - Qian Wang
- Department of Diagnostic Imaging, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China
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Cotta GC, Teixeira dos Santos RC, Costa GMJ, Lacerda SMDSN. Reporter Alleles in hiPSCs: Visual Cues on Development and Disease. Int J Mol Sci 2024; 25:11009. [PMID: 39456792 PMCID: PMC11507014 DOI: 10.3390/ijms252011009] [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: 08/30/2024] [Revised: 10/05/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Reporter alleles are essential for advancing research with human induced pluripotent stem cells (hiPSCs), notably in developmental biology and disease modeling. This study investigates the state-of-the-art gene-editing techniques tailored for generating reporter alleles in hiPSCs, emphasizing their effectiveness in investigating cellular dynamics and disease mechanisms. Various methodologies, including the application of CRISPR/Cas9 technology, are discussed for accurately integrating reporter genes into the specific genomic loci. The synthesis of findings from the studies utilizing these reporter alleles reveals insights into developmental processes, genetic disorder modeling, and therapeutic screening, consolidating the existing knowledge. These hiPSC-derived models demonstrate remarkable versatility in replicating human diseases and evaluating drug efficacy, thereby accelerating translational research. Furthermore, this review addresses challenges and future directions in refining the reporter allele design and application to bolster their reliability and relevance in biomedical research. Overall, this investigation offers a comprehensive perspective on the methodologies, applications, and implications of reporter alleles in hiPSC-based studies, underscoring their essential role in advancing both fundamental scientific understanding and clinical practice.
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Affiliation(s)
| | | | | | - Samyra Maria dos Santos Nassif Lacerda
- Laboratory of Cellular Biology, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, 31270-901 Belo Horizonte, Brazil; (G.C.C.); (R.C.T.d.S.); (G.M.J.C.)
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3
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Oh HR, Ko MK, Son D, Ki YW, Kim SI, Lee SY, Kang KW, Cheon GJ, Hwang DW, Youn H. Activated Natural Killer Cell Inoculation Alleviates Fibrotic Liver Pathology in a Carbon Tetrachloride-Induced Liver Cirrhosis Mouse Model. Biomedicines 2023; 11:1090. [PMID: 37189708 PMCID: PMC10135902 DOI: 10.3390/biomedicines11041090] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/23/2023] [Accepted: 03/29/2023] [Indexed: 05/17/2023] Open
Abstract
Activated hepatic stellate cells (HSCs) play a detrimental role in liver fibrosis progression. Natural killer (NK) cells are known to selectively recognize abnormal or transformed cells via their receptor activation and induce target cell apoptosis and, therefore, can be used as a potential therapeutic strategy for liver cirrhosis. In this study, we examined the therapeutic effects of NK cells in the carbon tetrachloride (CCl4)-induced liver cirrhosis mouse model. NK cells were isolated from the mouse spleen and expanded in the cytokine-stimulated culture medium. Natural killer group 2, member D (NKG2D)-positive NK cells were significantly increased after a week of expansion in culture. The intravenous injection of NK cells significantly alleviated liver cirrhosis by reducing collagen deposition, HSC marker activation, and macrophage infiltration. For in vivo imaging, NK cells were isolated from codon-optimized luciferase-expressing transgenic mice. Luciferase-expressing NK cells were expanded, activated and administrated to the mouse model to track them. Bioluminescence images showed increased accumulation of the intravenously inoculated NK cells in the cirrhotic liver of the recipient mouse. In addition, we conducted QuantSeq 3' mRNA sequencing-based transcriptomic analysis. From the transcriptomic analysis, 33 downregulated genes in the extracellular matrix (ECM) and 41 downregulated genes involved in the inflammatory response were observed in the NK cell-treated cirrhotic liver tissues from the 1532 differentially expressed genes (DEGs). This result indicated that the repetitive administration of NK cells alleviated the pathology of liver fibrosis in the CCl4-induced liver cirrhosis mouse model via anti-fibrotic and anti-inflammatory mechanisms. Taken together, our research demonstrated that NK cells could have therapeutic effects in a CCl4-induced liver cirrhosis mouse model. In particular, it was elucidated that extracellular matrix genes and inflammatory response genes, which were mainly affected after NK cell treatment, could be potential targets.
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Affiliation(s)
- Ho Rim Oh
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Min Kyung Ko
- Research & Development Center, THERABEST, Co., Ltd., Seoul 06656, Republic of Korea
| | - Daehee Son
- Research & Development Center, THERABEST, Co., Ltd., Seoul 06656, Republic of Korea
| | - Young Wook Ki
- Research & Development Center, THERABEST, Co., Ltd., Seoul 06656, Republic of Korea
| | - Shin-Il Kim
- Research & Development Center, THERABEST, Co., Ltd., Seoul 06656, Republic of Korea
| | - Seok-Yong Lee
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Cancer Imaging Center, Seoul National University Hospital, Seoul 03080, Republic of Korea
| | - Keon Wook Kang
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Gi Jeong Cheon
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Do Won Hwang
- Research & Development Center, THERABEST, Co., Ltd., Seoul 06656, Republic of Korea
| | - Hyewon Youn
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Cancer Imaging Center, Seoul National University Hospital, Seoul 03080, Republic of Korea
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Zhang L, Gong M, Lei S, Cui C, Liu Y, Xiao S, Kang X, Sun T, Xu Z, Zhou C, Zhang S, Zhang D. Targeting visualization of malignant tumor based on the alteration of DWI signal generated by hTERT promoter-driven AQP1 overexpression. Eur J Nucl Med Mol Imaging 2022; 49:2310-2322. [PMID: 35044495 DOI: 10.1007/s00259-022-05684-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 01/09/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE To specifically diagnose malignant tumors in DWI using the human telomerase reverse transcriptase (hTERT) promoter-driven AQP1 expression. METHODS The human telomerase reverse transcriptase (hTERT) promoter-driven AQP1 gene overexpression lentivirus system (hTERT-AQP1) and cytomegalovirus (CMV) promoter-driven AQP1 gene overexpression lentivirus system (CMV-AQP1) were prepared, and transduced into telomerase-positive and -negative cells. The AQP1 expression and DWI signal intensity (SI) change in transduced cells were analyzed. Balb/C nude mice subcutaneous xenograft models derived from lentivirus-transduced telomerase-positive and -negative cells were used to evaluate AQP1 expression and DWI SI change in vivo. We further established another group of subcutaneous xenograft model using pristine telomerase-positive and -negative cells, followed by injecting the lentiviral vectors intratumorally or intravenously, to determine the malignant tumor-targeted imaging of hTERT-AQP1. RESULTS The hTERT-AQP1 and CMV-AQP1 were successfully prepared. After transduction, hTERT-AQP1 could induce the specific overexpression of AQP1 in telomerase-positive cells. Compared with untransduced cells, all CMV-AQP1-pretransduced cells and hTERT-AQP1-pretransduced telomerase-positive cells showed decreased SI and increased apparent diffusion coefficient (ADC) in DWI, while hTERT-AQP1-pretransduced telomerase-negative cells showed no obvious SI and ADC change. Correspondingly, hTERT-AQP1-transduced telomerase-positive tumors and CMV-AQP1-transduced telomerase-positive and -negative tumors showed decreased DWI SI and increased ADC, while hTERT-AQP1-transduced telomerase-negative tumor had no SI and ADC changes. After intratumoral or intravenous injection, CMV-AQP1 could upregulate AQP1 expression and induce DWI SI and ADC alteration in both telomerase-positive and -negative tumors, while hTERT-AQP1 worked in telomerase-positive tumors specifically. CONCLUSION Cancers can be specifically visualized based on the DWI signal alteration which triggered by hTERT-AQP1 lentivirus system that combined AQP1 gene and hTERT promoter.
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Affiliation(s)
- Liang Zhang
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Mingfu Gong
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China.
| | - Sheng Lei
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Chun Cui
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Yun Liu
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Shilin Xiao
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Xun Kang
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Tao Sun
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Zhongsheng Xu
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Chunyu Zhou
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Si Zhang
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China
| | - Dong Zhang
- Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao street Shapingba district, Chongqing, China.
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Abstract
Apoptosis is a process in which cells are genetically regulated to cause a series of changes in morphology and metabolic activity, which ultimately lead to cell death. Apoptosis plays a vital role in the entire life cycle of an organism. Too much or too little apoptosis can cause a variety of diseases. Therefore, efficient and convenient methods for detecting apoptosis are necessary for clinical treatment and drug development. Traditional methods for detecting apoptosis may cause damage to the body during sample collection, such as for flow cytometry analysis. So it is necessary to monitor apoptosis without invasion in vivo. Optical imaging technique provides a more sensitive and economical way for apoptosis visualization. A subset of engineered reporter genes based on fluorescent proteins or luciferases are currently developed to monitor the dynamic changes in apoptotic markers, such as activation of caspases and exposure of phosphatidylserine on the surface of dying cells. These reporters detect apoptosis when cells have not undergone significant morphological changes, providing conditions for early diagnosis of tumors. In addition, these reporters show considerable value in high-throughput screening of apoptosis-related drugs and evaluation of their efficacy in treating tumors. In this review, we will discuss the recent research progress in the optical imaging of apoptosis based on the genetically encoded reporter genes.
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Liu C, Han D, Liang P, Li Y, Cao F. The Current Dilemma and Breakthrough of Stem Cell Therapy in Ischemic Heart Disease. Front Cell Dev Biol 2021; 9:636136. [PMID: 33968924 PMCID: PMC8100527 DOI: 10.3389/fcell.2021.636136] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 03/29/2021] [Indexed: 01/15/2023] Open
Abstract
Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Stem cell transplantation has become a promising approach for the treatment of IHD in recent decades. It is generally recognized that preclinical cell-based therapy is effective and have yielded encouraging results, which involves preventing or reducing myocardial cell death, inhibiting scar formation, promoting angiogenesis, and improving cardiac function. However, clinical studies have not yet achieved a desired outcome, even multiple clinical studies showing paradoxical results. Besides, many fundamental puzzles remain to be resolved, for example, what is the optimal delivery timing and approach? Additionally, limited cell engraftment and survival, challenging cell fate monitoring, and not fully understood functional mechanisms are defined hurdles to clinical translation. Here we review some of the current dilemmas in stem cell-based therapy for IHD, along with our efforts and opinions on these key issues.
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Affiliation(s)
- Chuanbin Liu
- Medical School of Chinese PLA, Beijing, China
- The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing, China
| | - Dong Han
- The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasond, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yang Li
- Department of Cardiology, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Feng Cao
- The Second Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Disease, Beijing, China
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Song Y, Xu Z, Wang F. Genetically Encoded Reporter Genes for MicroRNA Imaging in Living Cells and Animals. MOLECULAR THERAPY. NUCLEIC ACIDS 2020; 21:555-567. [PMID: 32721876 PMCID: PMC7390858 DOI: 10.1016/j.omtn.2020.06.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/12/2020] [Accepted: 06/24/2020] [Indexed: 12/13/2022]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by base paring with the complementary sequences of the target mRNAs, and then exert their function through degrading mRNA or inhibiting protein translation. They play a significant role as a regulatory factor in biological processes of organism development, cell proliferation, differentiation, and cell death. Some of the traditional methods for studying miRNAs, such as northern blot, real-time PCR, or microarray, have been extensively used to investigate the biological properties and expression patterns of miRNAs. However, these methods often require considerable time, cell samples, and the design of effective primers or specific probes. Therefore, in order to gain a deeper understanding of the role of miRNAs in biological processes and accelerate the clinical application of miRNAs in the field of disease treatment, non-invasive, sensitive, and efficient imaging methods are needed to visualize the dynamic expression of miRNAs in living cells and animals. In this study, we reviewed the recent progress in the genetically encoded reporter genes for miRNA imaging.
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Affiliation(s)
- Yingzhuang Song
- Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Zhijing Xu
- Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
| | - Fu Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China.
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Wang WH, Shen CY, Chien YC, Chang WS, Tsai CW, Lin YH, Hwang JJ. Validation of Enhancing Effects of Curcumin on Radiotherapy with F98/ FGT Glioblastoma-Bearing Rat Model. Int J Mol Sci 2020; 21:ijms21124385. [PMID: 32575632 PMCID: PMC7352749 DOI: 10.3390/ijms21124385] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 06/15/2020] [Accepted: 06/16/2020] [Indexed: 12/17/2022] Open
Abstract
Glioblastoma, the most common and aggressive brain tumor with low survival rate, is difficult to be cured by neurosurgery or radiotherapy. Mounting evidence has reported the anti-inflammatory and anticancer effects of curcumin on several types of cancer in preclinical studies and clinical trials. To our knowledge, there is no platform or system that could be used to effectively and real-timely evaluate the therapeutic efficacy of curcumin for glioblastoma multiforme (GBM). In this study, we constructed a lentivirus vector with triple-reporter genes (Fluc/GFP/tk) and transduced into rat F98 glioblastoma cells to establish an orthotopic F98/FGT glioma-bearing rat model. In the model, the therapeutic efficacies for curcumin alone, radiation alone, and their combination were evaluated via noninvasive bioluminescent imaging and overall survival measurements. At the cell level, curcumin is capable of causing a G2/M cell cycle arrest and sensitizing the F98 cells to radiation. In animal model, curcumin synergistically enhances the effects of radiotherapy on suppressing the growth of both transplanted glioma cells and in situ brain tumors, and extending the overall survival periods longer than those of curcumin alone and radiation alone treatments. In conclusion, we have demonstrated that curcumin may serve as a novel radiosensitizer to combine with radiotherapy using the triple-reporter F98/FGT animal model for effective and simultaneous evaluation of therapeutic efficacy.
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Affiliation(s)
- Wei-Hsun Wang
- Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 500, Taiwan;
- Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan
| | - Chao-Yu Shen
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; or
- Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Yi-Chun Chien
- Department of Medical Imaging and Radiological Sciences, I-Shou University, Jiaosu Village, Kaohsiung 824, Taiwan;
- School of Medicine, I-Shou University, Jiaosu Village, Kaohsiung 824, Taiwan
| | - Wen-Shin Chang
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 402, Taiwan; (W.-S.C.); (C.-W.T.)
| | - Chia-Wen Tsai
- Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 402, Taiwan; (W.-S.C.); (C.-W.T.)
| | - Yi-Hsien Lin
- Division of Radiotherapy, Cheng Hsin General Hospital, No. 45, Cheng Hsin St, Beitou, Taipei 112, Taiwan
- School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
- Correspondence: (Y.-H.L.); (J.-J.H.); Tel.: +88-622-826-4400 (ext. 5750) (Y.-H.L.); +88-642-473-9595 (ext. 32138) (J.-J.H.); Fax: +88-622-826-4524 (Y.-H.L.); +88-642-324-8186 (J.-J.H.)
| | - Jeng-Jong Hwang
- Department of Medical Imaging, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo North Road, Taichung 402, Taiwan
- Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 112, Taiwan
- Correspondence: (Y.-H.L.); (J.-J.H.); Tel.: +88-622-826-4400 (ext. 5750) (Y.-H.L.); +88-642-473-9595 (ext. 32138) (J.-J.H.); Fax: +88-622-826-4524 (Y.-H.L.); +88-642-324-8186 (J.-J.H.)
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Summer D, Petrik M, Mayr S, Hermann M, Kaeopookum P, Pfister J, Klingler M, Rangger C, Haas H, Decristoforo C. Hybrid Imaging Agents for Pretargeting Applications Based on Fusarinine C-Proof of Concept. Molecules 2020; 25:E2123. [PMID: 32370017 PMCID: PMC7249120 DOI: 10.3390/molecules25092123] [Citation(s) in RCA: 4] [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: 04/17/2020] [Revised: 04/29/2020] [Accepted: 04/29/2020] [Indexed: 12/16/2022] Open
Abstract
Hybrid imaging combining the beneficial properties of radioactivity and optical imaging within one imaging probe has gained increasing interest in radiopharmaceutical research. In this study, we modified the macrocyclic gallium-68 chelator fusarinine C (FSC) by conjugating a fluorescent moiety and tetrazine (Tz) moieties. The resulting hybrid imaging agents were used for pretargeting applications utilizing click reactions with a trans-cyclooctene (TCO) tagged targeting vector for a proof of principle both in vitro and in vivo. Starting from FSC, the fluorophores Sulfocyanine-5, Sulfocyanine-7, or IRDye800CW were conjugated, followed by introduction of one or two Tz motifs, resulting in mono and dimeric Tz conjugates. Evaluation included fluorescence microscopy, binding studies, logD, protein binding, in vivo biodistribution, µPET (micro-positron emission tomography), and optical imaging (OI) studies. 68Ga-labeled conjugates showed suitable hydrophilicity, high stability, and specific targeting properties towards Rituximab-TCO pre-treated CD20 expressing Raji cells. Biodistribution studies showed fast clearance and low accumulation in non-targeted organs for both SulfoCy5- and IRDye800CW-conjugates. In an alendronate-TCO based bone targeting model the dimeric IRDye800CW-conjugate resulted in specific targeting using PET and OI, superior to the monomer. This proof of concept study showed that the preparation of FSC-Tz hybrid imaging agents for pretargeting applications is feasible, making such compounds suitable for hybrid imaging applications.
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Affiliation(s)
- Dominik Summer
- Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria; (D.S.); (S.M.); (P.K.); (J.P.); (M.K.); (C.R.)
| | - Milos Petrik
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, 772-00 Olomouc, Czech Republic;
| | - Sonja Mayr
- Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria; (D.S.); (S.M.); (P.K.); (J.P.); (M.K.); (C.R.)
| | - Martin Hermann
- Department of Anaesthesia and Intensive Care, Medical University Innsbruck, A-6020 Innsbruck, Austria;
| | - Piriya Kaeopookum
- Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria; (D.S.); (S.M.); (P.K.); (J.P.); (M.K.); (C.R.)
| | - Joachim Pfister
- Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria; (D.S.); (S.M.); (P.K.); (J.P.); (M.K.); (C.R.)
| | - Maximilian Klingler
- Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria; (D.S.); (S.M.); (P.K.); (J.P.); (M.K.); (C.R.)
| | - Christine Rangger
- Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria; (D.S.); (S.M.); (P.K.); (J.P.); (M.K.); (C.R.)
| | - Hubertus Haas
- Institute of Molecular Biology, Medical University Innsbruck, A-6020 Innsbruck, Austria;
| | - Clemens Decristoforo
- Department of Nuclear Medicine, Medical University Innsbruck, A-6020 Innsbruck, Austria; (D.S.); (S.M.); (P.K.); (J.P.); (M.K.); (C.R.)
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10
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Pan CT, Chang WH, Kumar A, Singh SP, Kaushik AC, Sharma J, Long ZJ, Wen ZH, Mishra SK, Yen CK, Chaudhary RK, Shiue YL. Nanoparticles-mediated Brain Imaging and Disease Prognosis by Conventional as well as Modern Modal Imaging Techniques: a Comparison. Curr Pharm Des 2020; 25:2637-2649. [PMID: 31603057 DOI: 10.2174/1381612825666190709220139] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 07/02/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND Multimodal imaging plays an important role in the diagnosis of brain disorders. Neurological disorders need to be diagnosed at an early stage for their effective treatment as later, it is very difficult to treat them. If possible, diagnosing at an early stage can be much helpful in curing the disease with less harm to the body. There is a need for advanced and multimodal imaging techniques for the same. This paper provides an overview of conventional as well as modern imaging techniques for brain diseases, specifically for tumor imaging. In this paper, different imaging modalities are discussed for tumor detection in the brain along with their advantages and disadvantages. Conjugation of two and more than two modalities provides more accurate information rather than a single modality. They can monitor and differentiate the cellular processes of normal and diseased condition with more clarity. The advent of molecular imaging, including reporter gene imaging, has opened the door of more advanced noninvasive detection of brain tumors. Due to specific optical properties, semiconducting polymer-based nanoparticles also play a pivotal role in imaging tumors. OBJECTIVE The objective of this paper is to review nanoparticles-mediated brain imaging and disease prognosis by conventional as well as modern modal imaging techniques. CONCLUSION We reviewed in detail various medical imaging techniques. This paper covers recent developments in detail and elaborates a possible research aspect for the readers in the field.
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Affiliation(s)
- Cheng-Tang Pan
- Department of Mechanical and Electro-Mechanical Engineering, National Sun Yat-Sen University, Kaohsiung City 804, Taiwan.,Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung City 804, Taiwan
| | - Wei-Hsi Chang
- Department of Emergency Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Ajay Kumar
- Department of Mechanical and Electro-Mechanical Engineering, National Sun Yat-Sen University, Kaohsiung City 804, Taiwan.,Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung City 804, Taiwan
| | - Satya P Singh
- School of EEE, Nanyang Technological University, Nanyang Ave, Singapore
| | - Aman Chandra Kaushik
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, ShanghaiJia Tong University, Shanghai 200240, China
| | - Jyotsna Sharma
- Amity School of Applied Sciences, Amity University Haryana, Gurugram-122413, Manesai, Panchgaon, Haryana, India
| | - Zheng-Jing Long
- Department of Emergency Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Zhi-Hong Wen
- Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Sunil Kumar Mishra
- Patronage Institute of Management Studies, Greater Noida, Uttar Pradesh, India
| | - Chung-Kun Yen
- Department of Mechanical and Electro-Mechanical Engineering, National Sun Yat-Sen University, Kaohsiung City 804, Taiwan
| | - Ravi Kumar Chaudhary
- School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pardesh, India, India
| | - Yow-Ling Shiue
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung City 804, Taiwan
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11
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Liu X, Huang H, Gao Y, Zhou L, Yang J, Li X, Li Y, Zhao H, Su S, Ke C, Pei Z. Visualization of gene therapy with a liver cancer-targeted adeno-associated virus 3 vector. J Cancer 2020; 11:2192-2200. [PMID: 32127946 PMCID: PMC7052912 DOI: 10.7150/jca.39579] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 01/03/2020] [Indexed: 12/13/2022] Open
Abstract
Background: To evaluate the feasibility of a self-complementing recombinant adeno-associated virus 3 (scrAAV3) vector targeting liver cancer and non-invasively monitor gene therapy of liver cancer. Materials and methods: An scrAAV3-HSV1-TK-kallistatin (ATK) gene drug was constructed, which contained the herpes virus thymidine kinase (HSV1-TK) reporter gene and human endogenous angiogenesis inhibitor (kallistatin) gene for non-invasive imaging of gene expression. Subcutaneous xenografted tumors of hepatoma in nude mice were generated for positron emission tomography/computed tomography (PET/CT) imaging. The ATK group was injected with the ATK gene through the tail vein, and an imaging agent was injected 2 weeks later. PET/CT imaging was performed at 1 hour after injection of the imaging agent. The control group was injected with phosphate-buffered saline at the same volume as the ATK gene drug. HE staining is used for pathological observation of tumor sections. HSV1-TK and kallistatin expression was identified by immunofluorescence, real-time quantitative PCR, and western blotting. Results: Radioactivity on PET/CT images was significantly higher in the ATK group compared with the control group. 18F-FHBG uptake values of left forelegs in ATK and control groups were 0.591±0.151% and 0.017 ± 0.011% ID/g (n=5), respectively (P<0.05). After injection of the ATK gene drug, mRNA and protein expression of HSV1-TK and kallistatin in subcutaneous xenograft tumors was detected successfully. In vitro analysis demonstrated significant differences in the expression of HSV1-TK and kallistatin between ATK and control groups (P<0.05). Conclusions: The scrAAV3 vector has a strong liver cancer-targeting ability, and the ATK gene drug can be used for targeted and non-invasive monitoring of liver cancer gene therapy.
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Affiliation(s)
- Xusheng Liu
- Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Hanling Huang
- Health management center, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Yan Gao
- Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Lumeng Zhou
- Postgraduate Training Base of Taihe Hospital, Jinzhou Medical University, Jinzhou, 121000, China
| | - Jianwei Yang
- Postgraduate Training Base of Taihe Hospital, Jinzhou Medical University, Jinzhou, 121000, China
| | - Xiaohui Li
- Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Yang Li
- Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Haiwen Zhao
- Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Shanchun Su
- Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Changbin Ke
- Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
| | - Zhijun Pei
- Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China
- Hubei Key Laboratory of WudangLocal Chinese Medicine Research, Shiyan, 442000, China
- Hubei Key Laboratory of Embryonic Stem Cell Research, Shiyan, 442000, China
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12
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Abstract
Molecular imaging enables both spatial and temporal understanding of the complex biologic systems underlying carcinogenesis and malignant spread. Single-photon emission tomography (SPECT) is a versatile nuclear imaging-based technique with ideal properties to study these processes in vivo in small animal models, as well as to identify potential drug candidates and characterize their antitumor action and potential adverse effects. Small animal SPECT and SPECT-CT (single-photon emission tomography combined with computer tomography) systems continue to evolve, as do the numerous SPECT radiopharmaceutical agents, allowing unprecedented sensitivity and quantitative molecular imaging capabilities. Several of these advances, their specific applications in oncology as well as new areas of exploration are highlighted in this chapter.
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Affiliation(s)
- Benjamin L Franc
- Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, H2232, MC 5281, Stanford, CA, 94305-5105, USA.
| | - Youngho Seo
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA
| | - Robert Flavell
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA
| | - Carina Mari Aparici
- Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, H2232, MC 5281, Stanford, CA, 94305-5105, USA
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13
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In vivo imaging of TGFβ signalling components using positron emission tomography. Drug Discov Today 2019; 24:2258-2272. [DOI: 10.1016/j.drudis.2019.08.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 08/01/2019] [Accepted: 08/28/2019] [Indexed: 12/21/2022]
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14
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Brewer KD, Spitler R, Lee KR, Chan AC, Barrozo JC, Wakeel A, Foote CS, Machtaler S, Rioux J, Willmann JK, Chakraborty P, Rice BW, Contag CH, Bell CB, Rutt BK. Characterization of Magneto-Endosymbionts as MRI Cell Labeling and Tracking Agents. Mol Imaging Biol 2018; 20:65-73. [PMID: 28616842 DOI: 10.1007/s11307-017-1093-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE Magneto-endosymbionts (MEs) show promise as living magnetic resonance imaging (MRI) contrast agents for in vivo cell tracking. Here we characterize the biomedical imaging properties of ME contrast agents, in vitro and in vivo. PROCEDURES By adapting and engineering magnetotactic bacteria to the intracellular niche, we are creating magneto-endosymbionts (MEs) that offer advantages relative to passive iron-based contrast agents (superparamagnetic iron oxides, SPIOs) for cell tracking. This work presents a biomedical imaging characterization of MEs including: MRI transverse relaxivity (r 2) for MEs and ME-labeled cells (compared to a commercially available iron oxide nanoparticle); microscopic validation of labeling efficiency and subcellular locations; and in vivo imaging of a MDA-MB-231BR (231BR) human breast cancer cells in a mouse brain. RESULTS At 7T, r 2 relaxivity of bare MEs was higher (250 s-1 mM-1) than that of conventional SPIO (178 s-1 mM-1). Optimized in vitro loading of MEs into 231BR cells yielded 1-4 pg iron/cell (compared to 5-10 pg iron/cell for conventional SPIO). r 2 relaxivity dropped by a factor of ~3 upon loading into cells, and was on the same order of magnitude for ME-loaded cells compared to SPIO-loaded cells. In vivo, ME-labeled cells exhibited strong MR contrast, allowing as few as 100 cells to be detected in mice using an optimized 3D SPGR gradient-echo sequence. CONCLUSIONS Our results demonstrate the potential of magneto-endosymbionts as living MR contrast agents. They have r 2 relaxivity values comparable to traditional iron oxide nanoparticle contrast agents, and provide strong MR contrast when loaded into cells and implanted in tissue.
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Affiliation(s)
- Kimberly D Brewer
- Biomedical Translational Imaging Centre (BIOTIC), Halifax, Nova Scotia, Canada.,Radiology Department and Molecular Imaging Program (MIPS), Stanford University, Stanford, CA, USA
| | - Ryan Spitler
- Radiology Department and Molecular Imaging Program (MIPS), Stanford University, Stanford, CA, USA
| | | | | | | | | | | | - Steven Machtaler
- Radiology Department and Molecular Imaging Program (MIPS), Stanford University, Stanford, CA, USA
| | - James Rioux
- Biomedical Translational Imaging Centre (BIOTIC), Halifax, Nova Scotia, Canada.,Radiology Department and Molecular Imaging Program (MIPS), Stanford University, Stanford, CA, USA
| | - Juergen K Willmann
- Radiology Department and Molecular Imaging Program (MIPS), Stanford University, Stanford, CA, USA
| | | | | | - Christopher H Contag
- Radiology Department and Molecular Imaging Program (MIPS), Stanford University, Stanford, CA, USA
| | | | - Brian K Rutt
- Radiology Department and Molecular Imaging Program (MIPS), Stanford University, Stanford, CA, USA. .,Richard M. Lucas Center for Imaging, Stanford University School of Medicine, The Lucas Expansion, Room PS-064, 1201 Welch Road, Stanford, CA, 94305-5488, USA.
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15
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Li M, Wang Y, Liu M, Lan X. Multimodality reporter gene imaging: Construction strategies and application. Theranostics 2018; 8:2954-2973. [PMID: 29896296 PMCID: PMC5996353 DOI: 10.7150/thno.24108] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 03/06/2018] [Indexed: 12/11/2022] Open
Abstract
Molecular imaging has played an important role in the noninvasive exploration of multiple biological processes. Reporter gene imaging is a key part of molecular imaging. By combining with a reporter probe, a reporter protein can induce the accumulation of specific signals that are detectable by an imaging device to provide indirect information of reporter gene expression in living subjects. There are many types of reporter genes and each corresponding imaging technique has its own advantages and drawbacks. Fused reporter genes or single reporter genes with products detectable by multiple imaging modalities can compensate for the disadvantages and potentiate the advantages of each modality. Reporter gene multimodality imaging could be applied to trace implanted cells, monitor gene therapy, assess endogenous molecular events, screen drugs, etc. Although several types of multimodality imaging apparatus and multimodality reporter genes are available, more sophisticated detectors and multimodality reporter gene systems are needed.
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Affiliation(s)
- Mengting Li
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Hubei Province Key Laboratory of Molecular Imaging
| | - Yichun Wang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Hubei Province Key Laboratory of Molecular Imaging
| | - Mei Liu
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Hubei Province Key Laboratory of Molecular Imaging
| | - Xiaoli Lan
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Hubei Province Key Laboratory of Molecular Imaging
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16
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Wu ZJ, Tang FR, Ma ZW, Peng XC, Xiang Y, Zhang Y, Kang J, Ji J, Liu XQ, Wang XW, Xin HW, Ren BX. Oncolytic Viruses for Tumor Precision Imaging and Radiotherapy. Hum Gene Ther 2018; 29:204-222. [PMID: 29179583 DOI: 10.1089/hum.2017.189] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
In 2003 in China, Peng et al. invented the recombinant adenovirus expressing p53 (Gendicine) for clinical tumor virotherapy. This was the first clinically approved gene therapy and tumor virotherapy drug in the world. An oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor (Talimogene laherparepvec) was approved for melanoma treatment in the United States in 2015. Since then, oncolytic viruses have been attracting more and more attention in the field of oncology, and may become novel significant modalities of tumor precision imaging and radiotherapy after further improvement. Oncolytic viruses carrying reporter genes can replicate and express genes of interest selectively in tumor cells, thus improving in vivo noninvasive precision molecular imaging and radiotherapy. Here, the latest developments and molecular mechanisms of tumor imaging and radiotherapy using oncolytic viruses are reviewed, and perspectives are given for further research. Various types of tumors are discussed, and special attention is paid to gastrointestinal tumors.
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Affiliation(s)
- Zi J Wu
- 1 Laboratory of Oncology, Center for Molecular Medicine, Yangtze University , Jingzhou, China
- 2 Department of Medical Imaging, School of Medicine, Yangtze University , Jingzhou, China
- 3 The Second School of Clinical Medicine, Yangtze University , Jingzhou, China
| | - Feng R Tang
- 4 Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Initiative, National University of Singapore , Create Tower, Singapore
| | - Zhao-Wu Ma
- 1 Laboratory of Oncology, Center for Molecular Medicine, Yangtze University , Jingzhou, China
| | - Xiao-Chun Peng
- 1 Laboratory of Oncology, Center for Molecular Medicine, Yangtze University , Jingzhou, China
| | - Ying Xiang
- 1 Laboratory of Oncology, Center for Molecular Medicine, Yangtze University , Jingzhou, China
| | - Yanling Zhang
- 5 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou, China
- 6 School of Biotechnology, Southern Medical University , Guangzhou, China
| | - Jingbo Kang
- 7 The Navy General Hospital Tumor Diagnosis and Treatment Center , Beijing, China
| | - Jiafu Ji
- 8 Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute , Beijing, China
| | - Xiao Q Liu
- 1 Laboratory of Oncology, Center for Molecular Medicine, Yangtze University , Jingzhou, China
- 2 Department of Medical Imaging, School of Medicine, Yangtze University , Jingzhou, China
- 3 The Second School of Clinical Medicine, Yangtze University , Jingzhou, China
| | - Xian-Wang Wang
- 1 Laboratory of Oncology, Center for Molecular Medicine, Yangtze University , Jingzhou, China
| | - Hong-Wu Xin
- 1 Laboratory of Oncology, Center for Molecular Medicine, Yangtze University , Jingzhou, China
| | - Bo X Ren
- 2 Department of Medical Imaging, School of Medicine, Yangtze University , Jingzhou, China
- 3 The Second School of Clinical Medicine, Yangtze University , Jingzhou, China
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17
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Waiczies S, Niendorf T, Lombardi G. Labeling of cell therapies: How can we get it right? Oncoimmunology 2017; 6:e1345403. [PMID: 29123957 DOI: 10.1080/2162402x.2017.1345403] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 06/16/2017] [Accepted: 06/16/2017] [Indexed: 12/15/2022] Open
Abstract
Labeling cells for non-invasive tracking in vivo using magnetic resonance imaging (MRI) is an emerging hot topic garnering ever increasing attention, yet it is fraught with numerous methodological challenges, which merit careful attention. Several of the current procedures used to label cells for tracking by MRI take advantage of the intrinsic phagocytic nature of cells to engulf nanoparticles, though cells with low intrinsic phagocytic capacity are also commonly studied. Before we take the next steps towards administering such cells in vivo, it is essential to understand how the nanolabel is recognized, internalized, trafficked and distributed within the specific host cell. This is even more critical when contemplating labeling of cells that may ultimately be applied in vivo to patients in a therapeutic context.
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Affiliation(s)
- Sonia Waiczies
- Fluorine Magnetic Resonance Imaging in Immunology, Berlin Ultrahigh Field Facility, Max Delbrueck Center for Molecular Medicine, Berlin, Germany
| | - Thoralf Niendorf
- Fluorine Magnetic Resonance Imaging in Immunology, Berlin Ultrahigh Field Facility, Max Delbrueck Center for Molecular Medicine, Berlin, Germany
| | - Giovanna Lombardi
- Immunoregulation & Immunontervention, MRC Centre for Transplantation, King's College London, UK
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18
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Genetically encoded iron-associated proteins as MRI reporters for molecular and cellular imaging. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2017; 10. [DOI: 10.1002/wnan.1482] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 04/18/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023]
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19
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Brunker J, Yao J, Laufer J, Bohndiek SE. Photoacoustic imaging using genetically encoded reporters: a review. JOURNAL OF BIOMEDICAL OPTICS 2017; 22:2645343. [PMID: 28717818 DOI: 10.1117/1.jbo.22.7.070901] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 06/12/2017] [Indexed: 05/19/2023]
Abstract
Genetically encoded contrast in photoacoustic imaging (PAI) is complementary to the intrinsic contrast provided by endogenous absorbing chromophores such as hemoglobin. The use of reporter genes expressing absorbing proteins opens the possibility of visualizing dynamic cellular and molecular processes. This is an enticing prospect but brings with it challenges and limitations associated with generating and detecting different types of reporters. The purpose of this review is to compare existing PAI reporters and signal detection strategies, thereby offering a practical guide, particularly for the nonbiologist, to choosing the most appropriate reporter for maximum sensitivity in the biological and technological system of interest.
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Affiliation(s)
- Joanna Brunker
- University of Cambridge, Cancer Research UK Cambridge Institute and Department of Physics, Cambridge, United Kingdom
| | - Junjie Yao
- Duke University, Photoacoustic Imaging Lab, Department of Biomedical Engineering, Durham, North Carolina, United States
| | - Jan Laufer
- Martin-Luther-Universität Halle-Wittenberg, Institut für Physik, Halle (Saale), Germany
| | - Sarah E Bohndiek
- University of Cambridge, Cancer Research UK Cambridge Institute and Department of Physics, Cambridge, United Kingdom
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20
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Abstract
We have developed an imaging method designated as correlative light microscopy and block-face imaging (CoMBI), which contributes to improve the reliability of morphological analyses. This method can collect both the frozen sections and serial block-face images in a single specimen. The frozen section can be used for conventional light microscopic analysis to obtain 2-dimensional (2D) anatomical and molecular information, while serial block-face images can be used as 3-dimensional (3D) volume data for anatomical analysis. Thus, the sections maintain positional information in the specimen, and allows the correlation of 2D microscopic data and 3D volume data in a single specimen. The subjects can vary in size and type, and can cover most specimens encountered in biology. In addition, the required system for our method is characterized by cost-effectiveness. Here, we demonstrated the utility of CoMBI using specimens ranging in size from several millimeters to several centimeters, i.e., mouse embryos, human brainstem samples, and stag beetle larvae, and present successful correlation between the 2D light microscopic images and 3D volume data in a single specimen.
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21
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Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l -amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model. Biochem Biophys Res Commun 2017; 486:632-638. [PMID: 28322783 DOI: 10.1016/j.bbrc.2017.03.072] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 03/16/2017] [Indexed: 12/22/2022]
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22
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Kothari P, De BP, He B, Chen A, Chiuchiolo MJ, Kim D, Nikolopoulou A, Amor-Coarasa A, Dyke JP, Voss HU, Kaminsky SM, Foley CP, Vallabhajosula S, Hu B, DiMagno SG, Sondhi D, Crystal RG, Babich JW, Ballon D. Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors. Sci Rep 2017; 7:39594. [PMID: 28059103 PMCID: PMC5216390 DOI: 10.1038/srep39594] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 11/24/2016] [Indexed: 01/07/2023] Open
Abstract
Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications.
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Affiliation(s)
- P. Kothari
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - B. P. De
- Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA
| | - B. He
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - A. Chen
- Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA
| | - M. J. Chiuchiolo
- Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA
| | - D. Kim
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - A. Nikolopoulou
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - A. Amor-Coarasa
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - J. P. Dyke
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - H. U. Voss
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - S. M. Kaminsky
- Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA
| | - C. P. Foley
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - S. Vallabhajosula
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - B. Hu
- Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, USA
| | - S. G. DiMagno
- Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, USA
| | - D. Sondhi
- Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA
| | - R. G. Crystal
- Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA
| | - J. W. Babich
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
| | - D. Ballon
- Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA
- Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA
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23
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Lee CW, Choi SI, Lee SJ, Oh YT, Park G, Park NY, Yoon KA, Kim S, Kim D, Kim YH, Suh JS. The Effectiveness of Ferritin as a Contrast Agent for Cell Tracking MRI in Mouse Cancer Models. Yonsei Med J 2017; 58:51-58. [PMID: 27873495 PMCID: PMC5122652 DOI: 10.3349/ymj.2017.58.1.51] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 06/18/2016] [Accepted: 06/20/2016] [Indexed: 12/24/2022] Open
Abstract
PURPOSE We aimed to investigate the effectiveness of ferritin as a contrast agent and a potential reporter gene for tracking tumor cells or macrophages in mouse cancer models. MATERIALS AND METHODS Adenoviral human ferritin heavy chain (Ad-hFTH) was administrated to orthotopic glioma models and subcutaneous colon cancer mouse models using U87MG and HCT116 cells, respectively. Brain MR images were acquired before and daily for up to 6 days after the intracranial injection of Ad-hFTH. In the HCT116 tumor model, MR examinations were performed before and at 6, 24, and 48 h after intratumoral injection of Ad-hFTH, as well as before and every two days after intravenous injection of ferritin-labeled macrophages. The contrast effect of ferritin in vitro was measured by MR imaging of cell pellets. MRI examinations using a 7T MR scanner comprised a T1-weighted (T1w) spin-echo sequence, T2-weighted (T2w) relaxation enhancement sequence, and T2*-weighted (T2*w) fast low angle shot sequence. RESULTS Cell pellet imaging of Ad-hFTH in vitro showed a strong negatively enhanced contrast in T2w and T2*w images, presenting with darker signal intensity in high concentrations of Fe. T2w images of glioma and subcutaneous HCT116 tumor models showed a dark signal intensity around or within the Ad-hFTH tumor, which was distinct with time and apparent in T2*w images. After injection of ferritin-labeled macrophages, negative contrast enhancement was identified within the tumor. CONCLUSION Ferritin could be a good candidate as an endogenous MR contrast agent and a potential reporter gene that is capable of maintaining cell labeling stability and cellular safety.
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Affiliation(s)
- Chan Wha Lee
- Department of Medicine, The Graduate School of Yonsei University, Seoul, Korea
- Research Institute & Hospital, National Cancer Center, Goyang, Korea
| | - Sun Il Choi
- Research Institute & Hospital, National Cancer Center, Goyang, Korea
- Department of Life Science, Ewha Womans University, Seoul, Korea
| | - Sang Jin Lee
- Research Institute & Hospital, National Cancer Center, Goyang, Korea
- Department of System Cancer Science, Graduate School of Cancer Science & Policy, National Cancer Center, Goyang, Korea
| | - Young Taek Oh
- Research Institute & Hospital, National Cancer Center, Goyang, Korea
| | - Gunwoo Park
- Research Institute & Hospital, National Cancer Center, Goyang, Korea
| | - Na Yeon Park
- Department of System Cancer Science, Graduate School of Cancer Science & Policy, National Cancer Center, Goyang, Korea
| | - Kyoung Ah Yoon
- College of Veterinary Medicine, Konkuk University, Seoul, Korea
| | - Sunshin Kim
- Research Institute & Hospital, National Cancer Center, Goyang, Korea
| | - Daehong Kim
- Research Institute & Hospital, National Cancer Center, Goyang, Korea.
| | - Yun Hee Kim
- Research Institute & Hospital, National Cancer Center, Goyang, Korea
- Department of System Cancer Science, Graduate School of Cancer Science & Policy, National Cancer Center, Goyang, Korea.
| | - Jin Suck Suh
- Department of Medicine, The Graduate School of Yonsei University, Seoul, Korea
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24
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Price DN, McBride AA, Anton M, Kusewitt DF, Norenberg JP, MacKenzie DA, Thompson TA, Muttil P. Longitudinal Assessment of Lung Cancer Progression in Mice Using the Sodium Iodide Symporter Reporter Gene and SPECT/CT Imaging. PLoS One 2016; 11:e0169107. [PMID: 28036366 PMCID: PMC5201271 DOI: 10.1371/journal.pone.0169107] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 12/12/2016] [Indexed: 11/18/2022] Open
Abstract
Lung cancer has the highest mortality rate of any tissue-specific cancer in both men and women. Research continues to investigate novel drugs and therapies to mitigate poor treatment efficacy, but the lack of a good descriptive lung cancer animal model for preclinical drug evaluation remains an obstacle. Here we describe the development of an orthotopic lung cancer animal model which utilizes the human sodium iodide symporter gene (hNIS; SLC5A5) as an imaging reporter gene for the purpose of non-invasive, longitudinal tumor quantification. hNIS is a glycoprotein that naturally transports iodide (I-) into thyroid cells and has the ability to symport the radiotracer 99mTc-pertechnetate (99mTcO4-). A549 lung adenocarcinoma cells were genetically modified with plasmid or lentiviral vectors to express hNIS. Modified cells were implanted into athymic nude mice to develop two tumor models: a subcutaneous and an orthotopic xenograft tumor model. Tumor progression was longitudinally imaged using SPECT/CT and quantified by SPECT voxel analysis. hNIS expression in lung tumors was analyzed by quantitative real-time PCR. Additionally, hematoxylin and eosin staining and visual inspection of pulmonary tumors was performed. We observed that lentiviral transduction provided enhanced and stable hNIS expression in A549 cells. Furthermore, 99mTcO4- uptake and accumulation was observed within lung tumors allowing for imaging and quantification of tumor mass at two-time points. This study illustrates the development of an orthotopic lung cancer model that can be longitudinally imaged throughout the experimental timeline thus avoiding inter-animal variability and leading to a reduction in total animal numbers. Furthermore, our orthotopic lung cancer animal model is clinically relevant and the genetic modification of cells for SPECT/CT imaging can be translated to other tissue-specific tumor animal models.
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Affiliation(s)
- Dominique N. Price
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States of America
| | - Amber A. McBride
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States of America
- Sandia National Laboratory, Albuquerque, New Mexico, United States of America
| | - Martina Anton
- Institute of Molecular Immunology/Experimental Oncology and Therapy Research, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Donna F. Kusewitt
- Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America
| | - Jeffrey P. Norenberg
- New Mexico Center for Isotopes in Medicine, Albuquerque, New Mexico, United States of America
- University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, United States of America
| | - Debra A. MacKenzie
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States of America
| | - Todd A. Thompson
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States of America
- University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, United States of America
| | - Pavan Muttil
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States of America
- University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, United States of America
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Qin X, Hu X, Wu C, Cai M, Li Z, Zhang L, Lin L, Huang W, Zhu K. Hepatocellular Carcinoma Cells Carrying a Multimodality Reporter Gene for Fluorescence, Bioluminescence, and Magnetic Resonance Imaging In Vitro and In Vivo. Acad Radiol 2016; 23:1422-1430. [PMID: 27641103 DOI: 10.1016/j.acra.2016.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Revised: 06/27/2016] [Accepted: 07/01/2016] [Indexed: 12/22/2022]
Abstract
RATIONALE AND OBJECTIVES The study aimed to evaluate the feasibility of imaging or tracking hepatocellular carcinoma cells by modifying these cells to carry a multimodality reporter gene, enabling fluorescence, bioluminescence, and magnetic resonance imaging (MRI) in vitro and in vivo. MATERIALS AND METHODS HepG2 cells were labeled with the enhanced green fluorescent protein (EGFP)/luciferase2/ferritin-the multimodality reporter gene (labeled HepG2 cells). The labeled and unlabeled HepG2 cells were cultured in vitro and then injected subcutaneously into mice as a hepatoma model in vivo. The expressions of EGFP, luciferase2, and ferritin in HepG2 cell suspensions and hepatoma model were investigated using fluorescence, bioluminescence, and MRI. RESULTS Individual HepG2 cells expressing EGFP were identified under blue laser excitation. The linear coefficient between the optical signal intensity of luciferase2 and the number of labeled cells was 0.993. MRI was used to distinguish the T2* signal of 2 × 107 cells/mL between the labeled (6.67 ± 1.88 ms) and unlabeled cells (10.66 ± 2.22 ms) (P = 0.034). In vivo, individual HepG2 cells expressing EGFP in frozen sections were observed. Labeled cells expressing luciferase2 have been detected since the second day after injection, and the bioluminescence increased with the tumor size. The T2* signal was significantly different between the labeled (6.04 ± 1.60 ms) and unlabeled cells (17.06 ± 2.17 ms) (P <0.001). CONCLUSIONS A multimodality reporter gene consisting of EGFP, luciferase2, and ferritin was successfully integrated into the HepG2 cell genome via a lentiviral vector and was highly expressed in the daughter cells. These cells could be detected by fluorescence, bioluminescence, and MRI in vitro and in vivo.
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Affiliation(s)
- Xiaoxiao Qin
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Road, Guangzhou 510260, Guangdong Province, China; Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Xiaojun Hu
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Chun Wu
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Interventional Radiology Institute, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Mingyue Cai
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Interventional Radiology Institute, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Zhengran Li
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Interventional Radiology Institute, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Lina Zhang
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Liteng Lin
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Interventional Radiology Institute, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Wensou Huang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Road, Guangzhou 510260, Guangdong Province, China
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Road, Guangzhou 510260, Guangdong Province, China.
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Shaikh F, Jacob A, Van Gestel F, Yaghoubi S. Molecular Imaging in Genetic Medicine. Cureus 2016; 8:e565. [PMID: 27186447 PMCID: PMC4866833 DOI: 10.7759/cureus.565] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 04/11/2016] [Indexed: 12/29/2022] Open
Abstract
The field of biomedical imaging has made significant advances in recent times. This includes extremely high-resolution anatomic imaging and functional imaging of physiologic and pathologic processes as well as novel modalities in optical imaging to evaluate molecular features within the cellular environment. The latter has made it possible to image phenotypic markers of various genotypes that are implicated in human development, behavior, and disease. This article discusses the role of molecular imaging in genetic and precision medicine.
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Affiliation(s)
- Faiq Shaikh
- Imaging Informatics, University of Pittsburgh Medical Center, Pittsburgh, PA. ; Molecular Imaging, Cellsight Technologies, Inc., San Francisco, CA
| | - Ayden Jacob
- Director of Translational Medicine, Nanoaxis LLC, Neuroscientist, Neuro-Nanotech Division, University of California, Department of Bioengineering ; UCSF Department of Interventional Radiology and Oncology
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Paproski RJ, Li Y, Barber Q, Lewis JD, Campbell RE, Zemp R. Validating tyrosinase homologue melA as a photoacoustic reporter gene for imaging Escherichia coli. JOURNAL OF BIOMEDICAL OPTICS 2015; 20:106008. [PMID: 26502231 DOI: 10.1117/1.jbo.20.10.106008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Accepted: 09/22/2015] [Indexed: 06/05/2023]
Abstract
To understand the pathogenic processes for infectious bacteria, appropriate research tools are required for replicating and characterizing infections. Fluorescence and bioluminescence imaging have primarily been used to image infections in animal models, but optical scattering in tissue significantly limits imaging depth and resolution. Photoacoustic imaging, which has improved depth-to-resolution ratio compared to conventional optical imaging, could be useful for visualizing melA-expressing bacteria since melA is a bacterial tyrosinase homologue which produces melanin. Escherichia coli-expressing melA was visibly dark in liquid culture. When melA-expressing bacteria in tubes were imaged with a VisualSonics Vevo LAZR system, the signal-to-noise ratio of a 9×dilution sample was 55, suggesting that ∼20 bacteria cells could be detected with our system. Multispectral (680, 700, 750, 800, 850, and 900 nm) analysis of the photoacoustic signal allowed unmixing of melA-expressing bacteria from blood. To compare photoacoustic reporter gene melA (using Vevo system) with luminescent and fluorescent reporter gene Nano-lantern (using Bruker Xtreme In-Vivo system), tubes of bacteria expressing melA or Nano-lantern were submerged 10 mm in 1% Intralipid, spaced between <1 and 20 mm apart from each other, and imaged with the appropriate imaging modality. Photoacoustic imaging could resolve the two tubes of melA-expressing bacteria even when the tubes were less than 1 mm from each other, while bioluminescence and fluorescence imaging could not resolve the two tubes of Nano-lantern-expressing bacteria even when the tubes were spaced 10 mm from each other. After injecting 100-μL of melA-expressing bacteria in the back flank of a chicken embryo, photoacoustic imaging allowed visualization of melA-expressing bacteria up to 10-mm deep into the embryo. Photoacoustic signal from melA could also be separated from deoxy- and oxy-hemoglobin signal observed within the embryo and chorioallantoic membrane. Our results suggest that melA is a useful photoacoustic reporter gene for visualizing bacteria, and further work incorporating photoacoustic reporters into infectious bacterial strains is warranted.
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Affiliation(s)
- Robert J Paproski
- University of Alberta, Department of Electrical and Computer Engineering, Donadeo Innovation Centre for Engineering, 9211-116 Street, Edmonton, Alberta T6G 1H9, CanadabUniversity of Alberta, Department of Oncology, Katz Group Centre, 114 Street & 87 Avenu
| | - Yan Li
- University of Alberta, Department of Chemistry, 11227 Saskatchewan Drive, Edmonton, Alberta T6G 2G2, Canada
| | - Quinn Barber
- University of Alberta, Department of Electrical and Computer Engineering, Donadeo Innovation Centre for Engineering, 9211-116 Street, Edmonton, Alberta T6G 1H9, Canada
| | - John D Lewis
- University of Alberta, Department of Oncology, Katz Group Centre, 114 Street & 87 Avenue, Edmonton, Alberta T6G 2E1, Canada
| | - Robert E Campbell
- University of Alberta, Department of Chemistry, 11227 Saskatchewan Drive, Edmonton, Alberta T6G 2G2, Canada
| | - Roger Zemp
- University of Alberta, Department of Electrical and Computer Engineering, Donadeo Innovation Centre for Engineering, 9211-116 Street, Edmonton, Alberta T6G 1H9, Canada
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Barsanti C, Lenzarini F, Kusmic C. Diagnostic and prognostic utility of non-invasive imaging in diabetes management. World J Diabetes 2015; 6:792-806. [PMID: 26131322 PMCID: PMC4478576 DOI: 10.4239/wjd.v6.i6.792] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 12/23/2014] [Accepted: 04/14/2015] [Indexed: 02/05/2023] Open
Abstract
Medical imaging technologies are acquiring an increasing relevance to assist clinicians in diagnosis and to guide management and therapeutic treatment of patients, thanks to their non invasive and high resolution properties. Computed tomography, magnetic resonance imaging, and ultrasonography are the most used imaging modalities to provide detailed morphological reconstructions of tissues and organs. In addition, the use of contrast dyes or radionuclide-labeled tracers permits to get functional and quantitative information about tissue physiology and metabolism in normal and disease state. In recent years, the development of multimodal and hydrid imaging techniques is coming to be the new frontier of medical imaging for the possibility to overcome limitations of single modalities and to obtain physiological and pathophysiological measurements within an accurate anatomical framework. Moreover, the employment of molecular probes, such as ligands or antibodies, allows a selective in vivo targeting of biomolecules involved in specific cellular processes, so expanding the potentialities of imaging techniques for clinical and research applications. This review is aimed to give a survey of characteristics of main diagnostic non-invasive imaging techniques. Current clinical appliances and future perspectives of imaging in the diagnostic and prognostic assessment of diabetic complications affecting different organ systems will be particularly addressed.
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Molecular imaging of oncolytic viral therapy. MOLECULAR THERAPY-ONCOLYTICS 2015; 1:14007. [PMID: 27119098 PMCID: PMC4782985 DOI: 10.1038/mto.2014.7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2014] [Accepted: 03/09/2014] [Indexed: 01/25/2023]
Abstract
Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy.
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Abstract
OBJECTIVES Identify and discuss the nursing implications of personalized and precision oncology care. DATA SOURCES PubMed, CINAHL. CONCLUSION The implications in personalized and precision cancer nursing care include interpretation and clinical use of novel and personalized information including genetic testing; patient advocacy and support throughout testing, anticipation of results and treatment; ongoing chronic monitoring; and support for patient decision-making. Attention must also be given to the family and ethical implications of a personalized approach to care. IMPLICATIONS FOR NURSING PRACTICE Nurses face increasing challenges and opportunities in communication, support, and advocacy for patients given the availability of advanced testing, care and treatment in personalized and precision medicine. Nursing education and continuing education, clinical decision support, and health systems changes will be necessary to provide personalized multidisciplinary care to patients, in which nurses play a key role.
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Multi-wavelength photoacoustic imaging of inducible tyrosinase reporter gene expression in xenograft tumors. Sci Rep 2014; 4:5329. [PMID: 24936769 PMCID: PMC4060505 DOI: 10.1038/srep05329] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 06/02/2014] [Indexed: 12/17/2022] Open
Abstract
Photoacoustic imaging is an emerging hybrid imaging technology capable of breaking through resolution limits of pure optical imaging technologies imposed by optical-scattering to provide fine-resolution optical contrast information in deep tissues. We demonstrate the ability of multi-wavelength photoacoustic imaging to estimate relative gene expression distributions using an inducible expression system and co-register images with hemoglobin oxygen saturation estimates and micro-ultrasound data. Tyrosinase, the rate-limiting enzyme in melanin production, is used as a reporter gene owing to its strong optical absorption and enzymatic amplification mechanism. Tetracycline-inducible melanin expression is turned on via doxycycline treatment in vivo. Serial multi-wavelength imaging reveals very low estimated melanin expression in tumors prior to doxycycline treatment or in tumors with no tyrosinase gene present, but strong signals after melanin induction in tumors tagged with the tyrosinase reporter. The combination of new inducible reporters and high-resolution photoacoustic and micro-ultrasound technology is poised to bring a new dimension to the study of gene expression in vivo.
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Kooreman NG, Ransohoff JD, Wu JC. Tracking gene and cell fate for therapeutic gain. NATURE MATERIALS 2014; 13:106-9. [PMID: 24452344 PMCID: PMC4892936 DOI: 10.1038/nmat3868] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
Abstract
Parallel advances in molecular imaging modalities and in gene- and cell-based therapeutics have significantly advanced their respective fields. Here we discuss how the collaborative, preclinical intersection of these technologies will facilitate more informed and effective clinical translation of relevant therapies.
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Affiliation(s)
- Nigel G. Kooreman
- Stanford Cardiovascular Institute
- Departments of Medicine and Radiology (Molecular Imaging Program)
| | - Julia D. Ransohoff
- Stanford Cardiovascular Institute
- Departments of Medicine and Radiology (Molecular Imaging Program)
| | - Joseph C. Wu
- Stanford Cardiovascular Institute
- Departments of Medicine and Radiology (Molecular Imaging Program)
- Institute of Stem Cell Biology and Regenerative Medicine
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