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Ramos-Alvarez I, Jensen RT. The Important Role of p21-Activated Kinases in Pancreatic Exocrine Function. BIOLOGY 2025; 14:113. [PMID: 40001881 DOI: 10.3390/biology14020113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 01/10/2025] [Accepted: 01/15/2025] [Indexed: 02/27/2025]
Abstract
The p21-activated kinases (PAKs) are a conserved family of serine/threonine protein kinases, which are effectors for the Rho family GTPases, namely, Rac/Cdc42. PAKs are divided into two groups: group I (PAK1-3) and group II (PAK4-6). Both groups of PAKs have been well studied in apoptosis, protein synthesis, glucose homeostasis, growth (proliferation and survival) and cytoskeletal regulation, as well as in cell motility, proliferation and cycle control. However, little is known about the role of PAKs in the secretory tissues, including in exocrine tissue, such as the exocrine pancreas (except for islet function and pancreatic cancer growth). Recent studies have provided insights supporting the importance of PAKs in exocrine pancreas. This review summarizes the recent insights into the importance of PAKs in the exocrine pancreas by reviewing their presence and activation; the ability of GI hormones/neurotransmitters/GFs/post-receptor activators to activate them; the kinetics of their activation; the participation of exocrine-tissue PAKs in activating the main growth-signaling cascade; their roles in the stimulation of enzyme secretion; finally, their roles in pancreatitis. These insights suggest that PAKs could be more important in exocrine/secretory tissues than currently appreciated and that their roles should be explored in more detail in the future.
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Affiliation(s)
- Irene Ramos-Alvarez
- Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20812-1804, USA
| | - Robert T Jensen
- Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20812-1804, USA
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Nogareda Seoane Z, Mallón Araújo MC, Calatayud Cubes A, Barberán Corral C, Domínguez Novoa Y, Cousillas Castiñeira A, Martínez Lago N, de Matías Leralta JM, Pubul Nuñez V. Functional imaging in neuroendocrine tumors: assessment of molecular heterogeneity using [ 68Ga]Ga-DOTA-TOC and [ 18F]FDG PET/CT. Rev Esp Med Nucl Imagen Mol 2024; 43:500011. [PMID: 38643835 DOI: 10.1016/j.remnie.2024.500011] [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: 02/07/2024] [Accepted: 04/08/2024] [Indexed: 04/23/2024]
Abstract
OBJECTIVE The aim of the study was evaluate the diagnostic performance of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT in patients with histologically proven neuroendocrine tumors (NETs), as well as the correlation of the visualized findings with the tumor grade. MATERIAL AND METHODS We included 50 patients with NETs who underwent both [68Ga]Ga-DOTA-TOC and [18F]FDG PET/TC. The pooled sensitivity of both scans was compared, as well as [68Ga]Ga-DOTA-TOC and [18F]FDG for each tumor grade (grade 1/G1, grade 2/G2 and grade 3/G3). Also, the sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG as a function of the continuous variable Ki-67 was investigated. Finally, the number of lesions detected by both PET radiopharmaceuticals for each tumor grade was compared. RESULTS The pooled sensitivity of both PET/CT (96%) was higher than [68Ga]Ga-DOTA-TOC (84%) and [18F]FDG (44%) separately, with statistically significant differences. The sensitivity of [68Ga]Ga-DOTA-TOC was higher than [18F]FDG in both G1 (p = 0.004) and G2 (p < 0.001). In G3 the performance of both scans detected disease in 100% of this subgroup. The sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT correlated significantly with the Ki-67 proliferative index. In G2 patients the number of lesions detected with [68Ga]Ga-DOTA-TOC was higher than [18F]FDG. CONCLUSIONS The performance of both PET/CT, particularly in G2 and G3, demonstrates the molecular heterogeneity of metastatic NETs and contributes to the selection of a more appropriate treatment, particularly in those high-grade patients who may benefit from radionuclide therapy (PRRT).
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Affiliation(s)
- Z Nogareda Seoane
- Servicio de Medicina Nuclear, Hospital Clínico Universitario Santiago de Compostela, Spain.
| | - M C Mallón Araújo
- Servicio de Medicina Nuclear, Hospital Clínico Universitario Santiago de Compostela, Spain
| | - A Calatayud Cubes
- Servicio de Medicina Nuclear, Hospital Clínico Universitario Santiago de Compostela, Spain
| | - C Barberán Corral
- Servicio de Medicina Nuclear, Hospital Clínico Universitario Santiago de Compostela, Spain
| | - Y Domínguez Novoa
- Servicio de Digestivo, Hospital Clínico Universitario Santiago de Compostela, Spain
| | | | - N Martínez Lago
- Servicio de Oncología Médica, Hospital Hospitalario Universitario de Ferrol, Spain
| | - J M de Matías Leralta
- Servicio de Endocrinología y Nutrición, Hospital Universitario Lucus Augusti, Lugo, Spain
| | - V Pubul Nuñez
- Servicio de Medicina Nuclear, Hospital Clínico Universitario Santiago de Compostela, Spain
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Arrivi G, Specchia M, Pilozzi E, Rinzivillo M, Caruso D, Santangeli C, Prosperi D, Ascolese AM, Panzuto F, Mazzuca F. Diagnostic and Therapeutic Management of Primary Orbital Neuroendocrine Tumors (NETs): Systematic Literature Review and Clinical Case Presentation. Biomedicines 2024; 12:379. [PMID: 38397981 PMCID: PMC10886459 DOI: 10.3390/biomedicines12020379] [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: 12/01/2023] [Revised: 01/25/2024] [Accepted: 01/30/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND The ocular involvement of neuroendocrine neoplasms (NENs) is uncommon and mainly represented by metastases from gastrointestinal and lung neuroendocrine tumors. Primary orbital NENs are even less common and their diagnostic and therapeutic management is a challenge. METHODS A systematic review of the literature was conducted from 1966 to September 2023 on PubMed to identify articles on orbital NENs and to summarize their clinical-pathological features, diagnosis and therapeutic management. Furthermore, we presented a case of a locally advanced retro-orbital primary neuroendocrine tumor that was referred to the certified Center of Excellence of Sant'Andrea Hospital, La Sapienza University of Rome, Italy. RESULTS The final analysis included 63 records on orbital NENs and 11 records focused on primary orbital NENs. The localization was mostly unilateral and in the right orbit; proptosis or exophthalmos represented the initial symptoms. The diagnostic work-up and therapeutic management was discussed and a diagnostic algorithm for the suspicion of primary orbital NENs was proposed. CONCLUSIONS A multidisciplinary approach is required for the management of primary orbital NENs, emphasizing the importance of early referral to dedicated centers for prompt differential diagnosis, tailored treatment, and an improved quality of life and survival.
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Affiliation(s)
- Giulia Arrivi
- Oncology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, Grottarossa Street 1035-1039, 00189 Rome, Italy; (M.S.); (F.M.)
- Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, PhD School in Translational Medicine and Oncology, Sapienza University of Rome, 00189 Rome, Italy
| | - Monia Specchia
- Oncology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, Grottarossa Street 1035-1039, 00189 Rome, Italy; (M.S.); (F.M.)
| | - Emanuela Pilozzi
- Anatomia Patologica Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy;
| | - Maria Rinzivillo
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Digestive Disease Unit, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.R.); (F.P.)
| | - Damiano Caruso
- Radiology Unit, Department of Medical Surgical Sciences and Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy; (D.C.); (C.S.)
| | - Curzio Santangeli
- Radiology Unit, Department of Medical Surgical Sciences and Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy; (D.C.); (C.S.)
| | - Daniela Prosperi
- Nuclear Medicine Unit, Sant’Andrea University Hospital, 00189 Rome, Italy;
| | - Anna Maria Ascolese
- Radiotherapy Oncology Unit, Department of Surgical Medical Sciences and Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy;
| | - Francesco Panzuto
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Digestive Disease Unit, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.R.); (F.P.)
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy
| | - Federica Mazzuca
- Oncology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, Grottarossa Street 1035-1039, 00189 Rome, Italy; (M.S.); (F.M.)
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Kushwaha NK, Jaiswal P, Gupta P, Mishra N, Kulkarni SV. Primary hepatic functional neuroendocrine tumor in an elderly female: Case report. Clin Case Rep 2024; 12:e8382. [PMID: 38161645 PMCID: PMC10753622 DOI: 10.1002/ccr3.8382] [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: 11/08/2023] [Revised: 12/11/2023] [Accepted: 12/14/2023] [Indexed: 01/03/2024] Open
Abstract
Key Clinical Message Primary hepatic neuroendocrine tumor, an exceptionally rare subtype, poses a diagnostic challenge. Oncological resections should be considered, even in elderly patients after following protocolized pre-operative optimizations. Abstract Neuroendocrine tumors (NETs) are rare tumors that primarily develop in the gastrointestinal and respiratory tracts. While the liver is commonly affected by NET metastases, primary hepatic neuroendocrine tumors (PHNETs) are an exceptionally rare subtype. The characteristic slow growth and nonfunctional nature of PHNETs pose challenges in their diagnosis. Furthermore, PHNETs often exhibit a lack of unique radiological characteristics that differentiate them from other liver tumors, leading to frequent misdiagnosis as hepatocellular carcinoma. We performed left hepatectomy for PHNET in an elderly lady with prolonged stormy postoperative course. This case report of a PHNET highlights the importance of histopathology and immunohistochemistry in the diagnosis and emphasizes that oncological resection, if feasible, is the preferred treatment even in the elderly population.
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Affiliation(s)
| | | | - Prashant Gupta
- Army Hospital Research and Referral New DelhiNew DelhiIndia
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5
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Duan H, Iagaru A. Neuroendocrine Tumor Diagnosis: PET/MR Imaging. PET Clin 2023; 18:259-266. [PMID: 36707370 DOI: 10.1016/j.cpet.2022.11.008] [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] [Indexed: 01/26/2023]
Abstract
Imaging plays a critical role in the diagnosis and management of neuroendocrine tumors (NETs). The initial workup of the primary tumor, including its characterization, local and distant staging, defines subsequent treatment decisions. Functional imaging using hybrid systems, such as PET combined with computed tomography, has become the gold standard. As NETs majorly arise from the gastrointestinal system and metastasize primarily to the liver, simultaneous PET and MR imaging with its high soft tissue contrast might be a valuable clinical one-stop-shop whole-body imaging tool. This review presents the current status and challenges of PET/MR imaging for diagnosis of NETs.
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Affiliation(s)
- Heying Duan
- Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Stanford University, 300 Pasteur Drive, H2200, Stanford, CA 94305, USA
| | - Andrei Iagaru
- Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Stanford University, 300 Pasteur Drive, H2200, Stanford, CA 94305, USA.
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Detection of Bone Metastases by 68Ga-DOTA-SSAs and 18F-FDG PET/CT: A Two-Center Head-to-Head Study of Gastroenteropancreatic Neuroendocrine Neoplasms. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:1750132. [PMID: 36447752 PMCID: PMC9663244 DOI: 10.1155/2022/1750132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 10/08/2022] [Indexed: 11/10/2022]
Abstract
Purpose This study aimed to assess the efficacy of dual-tracer [68Ga-DOTA-somatostatin receptor analogs (SSAs) and 18F-fluorodeoxyglucose (FDG)] positron emission tomography/computed tomography (PET/CT) imaging for detecting bone metastases (BMs) in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Methods We retrospectively enrolled 74 GEP-NEN patients with BMs from two centers, who underwent dual-tracer PET/CT from January 2014 to March 2021. We compared and analyzed effectiveness of the dual PET/CT imaging techniques on the BMs, based on 18F-FDG and 68Ga-DOTA-SSAs. Specifically, we analyzed the imaging results using χ 2 tests for classification variables, paired-sample tests for number of BMs, Wilcoxon's signed rank test for number of lesions, and the Kruskal-Wallis test for standard uptake value (SUV) ratio comparison. The correlation of dual-tracer SUVmax with Ki-67 index was analyzed by Spearman's correlation coefficient. Results The detection efficiencies of dual-tracer PET/CT imaging in patients with different pathologies showed discordant for detecting liver metastases and BMs in group neuroendocrine tumor (NET) G3, 68Ga-DOTA-SSAs was better at detecting BMs for NET G3 (P=0.049 for SUVT/B and P=0.026 for the number of metastatic lesions). In addition, statistical significance was found among osteogenesis group, osteolysis group, and the no-change group (for bone SUVT/B value detected by 18F-FDG and Ki-67 index, osteogenesis group < osteolysis group; for bone SUVT/B detected by 68Ga-DOTA-SSAs, osteogenesis group > the no-change group). What is more, liver and bone SUVmax and Ki-67 index were positively correlated in 18F-FDG imaging (P < 0.001 for liver; P=0.002 for bone), and negatively correlated in 68Ga-DOTA-SSAs imaging (P < 0.001 for liver; P=0.039 for bone). Conclusions 68Ga-DOTA-SSAs was superior to 18F-FDG for detecting BMs in NET G1/G2 (well and moderately differentiated NETs), as well as in NET G3 (poorly differentiated NETs). Relatively good differentiation was observed in the osteogenesis group. In addition, dual-tracer PET/CT imaging results were observably correlated with tumor differentiation.
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Dai M, Mullins CS, Lu L, Alsfasser G, Linnebacher M. Recent advances in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Surg 2022; 14:383-396. [PMID: 35734622 PMCID: PMC9160679 DOI: 10.4240/wjgs.v14.i5.383] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/17/2022] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a rare group of tumors originating from neuroendocrine cells of the digestive system. Their incidence has increased over the last decades. The specific pathogenetic mechanisms underlying GEP-NEN development have not been completely revealed. Unfunctional GEP-NENs are usually asymptomatic; some grow slowly and thus impede early diagnosis, which ultimately results in a high rate of misdiagnosis. Therefore, many GEP-NEN patients present with later staged tumors. Motivated hereby, research attention for diagnosis and treatment for GEP-NENs increased in recent years. The result of which is great progress in clinical diagnosis and treatment. According to the most recent clinical guidelines, improved grading standards can accurately define poorly differentiated grade 3 neuroendocrine tumors and neuroendocrine carcinomas (NECs), which are subclassified into large and small cell NECs. Combining different functional imaging methods facilitates precise diagnosis. The expression of somatostatin receptors helps to predict prognosis. Genetic analyses of mutations affecting death domain associated protein (DAXX), multiple endocrine neoplasia type 1 (MEN 1), alpha thalassemia/intellectual disability syndrome X-linked (ATRX), retinoblastoma transcriptional corepressor 1 (RB 1), and mothers against decapentaplegic homolog 4 (SMAD 4) help distinguishing grade 3 NENs from poorly differentiated NECs. The aim of this review is to summarize the latest research progress on diagnosis and treatment of GEP-NENs.
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Affiliation(s)
- Meng Dai
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Christina S Mullins
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Lili Lu
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Guido Alsfasser
- Clinic of General Surgery, Rostock University Medical Center, 18057 Rostock, Germany
| | - Michael Linnebacher
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
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Rogasch JMM, Hofheinz F, van Heek L, Voltin CA, Boellaard R, Kobe C. Influences on PET Quantification and Interpretation. Diagnostics (Basel) 2022; 12:451. [PMID: 35204542 PMCID: PMC8871060 DOI: 10.3390/diagnostics12020451] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/06/2022] [Accepted: 02/08/2022] [Indexed: 01/21/2023] Open
Abstract
Various factors have been identified that influence quantitative accuracy and image interpretation in positron emission tomography (PET). Through the continuous introduction of new PET technology-both imaging hardware and reconstruction software-into clinical care, we now find ourselves in a transition period in which traditional and new technologies coexist. The effects on the clinical value of PET imaging and its interpretation in routine clinical practice require careful reevaluation. In this review, we provide a comprehensive summary of important factors influencing quantification and interpretation with a focus on recent developments in PET technology. Finally, we discuss the relationship between quantitative accuracy and subjective image interpretation.
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Affiliation(s)
- Julian M. M. Rogasch
- Department of Nuclear Medicine, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany;
- Berlin Institute of Health at Charité, Universitätsmedizin Berlin, 10178 Berlin, Germany
| | - Frank Hofheinz
- Institute of Radiopharmaceutical Cancer Research, Helmholtz Center Dresden-Rossendorf, 01328 Dresden, Germany;
| | - Lutz van Heek
- Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; (L.v.H.); (C.-A.V.)
| | - Conrad-Amadeus Voltin
- Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; (L.v.H.); (C.-A.V.)
| | - Ronald Boellaard
- Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam (CCA), Amsterdam University Medical Center, Free University Amsterdam, 1081 HV Amsterdam, The Netherlands;
| | - Carsten Kobe
- Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany; (L.v.H.); (C.-A.V.)
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Kaewput C, Vinjamuri S. Role of Combined 68Ga DOTA-Peptides and 18F FDG PET/CT in the Evaluation of Gastroenteropancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2022; 12:diagnostics12020280. [PMID: 35204371 PMCID: PMC8871217 DOI: 10.3390/diagnostics12020280] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 12/12/2022] Open
Abstract
This review article summarizes the role of combined 68Ga DOTA-peptides and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the evaluation of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Patients with GEP-NENs can initially present themselves to a gastroenterologist or endocrinologist rather than cancer specialist; hence, it is vital for a wider group of clinicians to be familiar with the range of tests available for the evaluation of these patients. The role of PET scanning by using 68Ga DOTA-peptides has a high sensitivity in the diagnosis of GEP-NENs and to guide patient selection for treatment with somatostatin analogues (SSA) and/or peptide receptor radionuclide therapy (PRRT). The loss of somatostatin receptor (SSTR) expression was found to be associated with an increased glucose metabolism in cells. However, the routine use of SSTR targeted radiotracers in combination with 18F-FDG to evaluate glucose utilization in GEP-NENs is still debatable. In our opinion, in patients with NENs, 18F-FDG PET should be performed in the case of a negative or slightly positive 68Ga DOTA-peptides PET scan for assessing the dedifferentiation status, to guide correct therapeutic strategy and to evaluate the prognosis. The approach of combined receptor and metabolic imaging can improve diagnostic accuracy, especially considering the heterogeneity of these lesions. Therefore, 68Ga DOTA-peptides and 18F-FDG PET should be considered complementary in patients with GEP-NENs.
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Affiliation(s)
- Chalermrat Kaewput
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Correspondence: ; Tel.: +66-2419-6220
| | - Sobhan Vinjamuri
- Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool L7 8XP, UK;
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Franquet E, Park H. Molecular imaging in oncology: Common PET/CT radiopharmaceuticals and applications. Eur J Radiol Open 2022; 9:100455. [DOI: 10.1016/j.ejro.2022.100455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/03/2022] [Accepted: 11/09/2022] [Indexed: 11/26/2022] Open
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Paiella S, Landoni L, Tebaldi S, Zuffante M, Salgarello M, Cingarlini S, D'Onofrio M, Parisi A, Deiro G, Manfrin E, Bianchi B, Montagnini G, Crinò SF, Bassi C, Salvia R. Dual-Tracer (68Ga-DOTATOC and 18F-FDG-)-PET/CT Scan and G1-G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Single-Center Retrospective Evaluation of 124 Nonmetastatic Resected Cases. Neuroendocrinology 2022; 112:143-152. [PMID: 33508821 DOI: 10.1159/000514809] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 01/28/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The combined use of 68gallium (68Ga)-DOTA-peptides and 18fluorine-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans in the workup of pancreatic neuroendocrine tumors (PanNETs) is controversial. This study aimed at assessing both tracers' capability to identify tumors and to assess its association with pathological predictors of recurrence. METHODS Prospectively collected, preoperative, dual-tracer PET/CT scan data of G1-G2, nonmetastatic, PanNETs that underwent surgery between January 2013 and October 2019 were retrospectively analyzed. RESULTS The final cohort consisted of 124 cases. There was an approximately equal distribution of males and females (50.8%/49.2%) and G1 and G2 tumors (49.2%/50.8%). The disease was detected in 122 (98.4%) and 64 (51.6%) cases by 68Ga-DOTATOC and by 18F-FDG PET/CT scans, respectively, with a combined sensitivity of 99.2%. 18F-FDG-positive examinations found G2 tumors more often than G1 (59.4 vs. 40.6%; p = 0.036), and 18F-FDG-positive PanNETs were larger than negative ones (median tumor size 32 mm, interquartile range [IQR] 21 vs. 26 mm, IQR 20; p = 0.019). The median Ki67 for 18F-FDG-positive and -negative examinations was 3 (IQR 4) and 2 (IQR 4), respectively (p = 0.029). At least 1 pathological predictor of recurrence was present in 74.6% of 18F-FDG-positive cases (vs. 56.7%; p = 0.039), whereas this was not found when dichotomizing the PanNETs by their dimensions (≤/>20 mm). None of the 2 tracers predicted nodal metastasis. The receiver operating characteristic curve analysis showed that 18F-FDG uptake higher than 4.2 had a sensitivity of 49.2% and specificity of 73.3% for differentiating G1 from G2 (AUC = 0.624, p = 0.009). CONCLUSION The complementary adoption of 68Ga-DOTATOC and 18F-FDG tracers may be valuable in the diagnostic workup of PanNETs despite not being a game-changer for the management of PanNETs ≤20 mm.
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Affiliation(s)
- Salvatore Paiella
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Luca Landoni
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Sarah Tebaldi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Michele Zuffante
- Nuclear Medicine Unit, Integrated University Hospital of Verona, Verona, Italy
| | - Matteo Salgarello
- Department of Nuclear Medicine, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy
| | - Sara Cingarlini
- Pancreas Institute, Oncology Unit, University of Verona Hospital Trust, Verona, Italy
| | - Mirko D'Onofrio
- Pancreas Institute, Radiology Unit, University of Verona Hospital Trust, Verona, Italy
| | - Alice Parisi
- Pancreas Institute, Department of Diagnostics and Public Health, Section of Pathology, University Verona Hospital Trust, Verona, Italy
| | - Giacomo Deiro
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Erminia Manfrin
- Pancreas Institute, Department of Diagnostics and Public Health, Section of Pathology, University Verona Hospital Trust, Verona, Italy
| | - Beatrice Bianchi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Greta Montagnini
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Stefano Francesco Crinò
- Pancreas Institute, Gastroenterology and Digestive Endoscopy Unit, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
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Current status and future prospects of PET-imaging applications in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Eur J Radiol 2021; 143:109932. [PMID: 34482177 DOI: 10.1016/j.ejrad.2021.109932] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 08/17/2021] [Accepted: 08/21/2021] [Indexed: 12/23/2022]
Abstract
Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous group of rare neoplasms with increasing incidence over the last decades. Localization of GEP-NETs and their metastases is a vital component for the implementation of accurate and patient-tailored treatment strategies. Addressing this challenge requires the employment of multidisciplinary imaging approaches, with hybrid positron emission tomography/computed tomography (PET/CT) imaging techniques standing at the forefront of this effort. GEP-NETs exhibit several pathophysiologic characteristics, which can serve as highly specific molecular targets that can be effectively visualized and quantified by means of PET-radiopharmaceuticals, facilitating diagnosis, accurate staging and efficient monitoring of treatment response. Furthermore, the capability for whole-body, in-vivo, non-invasive characterization of the molecular heterogeneity of the disease, provides strong prognostic information, while enabling the selection of patients suitable for precision-based theranostic approaches. The dual tracer (18F-FDG & 68Ga-DOTA-peptides) PET/CT imaging approach is the current optimal diagnostic imaging strategy, since it enables tumor localization, accurate staging, non-invasive whole-body total tumor burden characterization of disease heterogeneity, while providing strong prognostic information and guidance towards treatment strategy. Moreover, 64Cu-DOTATATE has been recently approved by FDA for SSTRs positive NETs, promising substantial diagnostic and logistical benefits. Furthermore, 18F-DOPA offers diagnostic capabilities for serotonin-secreting GEP-NETs which are not characterized by cell-surface over-expression of somatostatin receptors (SSTRs) and cannot be seen on morphological imaging. In addition, PET/CT with agents targeting the expression of glucagon-like peptide-1 receptor (GLP-R1) should be considered in cases of clinical suspicion for insulinomas that cannot be detected by morphological imaging or STTRs PET/CT imaging.
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Zhou J, Xie J, Pan Y, Zhang Y. Detection of Adult Pancreatoblastoma by 18F-FDG and 68Ga-DOTATATE PET/MR. Clin Nucl Med 2021; 46:671-674. [PMID: 33661203 DOI: 10.1097/rlu.0000000000003568] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
ABSTRACT A 36-year-old asymptomatic woman was incidentally found to have a huge mass in the pancreas by ultrasound during routine health screening. The mass was suspected of neuroendocrine tumor or solid pseudopapillary tumor by subsequent abdominal CT. 18F-FDG and 68Ga-DOTATATE PET/MR were acquired for presurgical assessment of the tumor invasion and malignant potential, which revealed intense FDG uptake and mild DOTATATE uptake. The tumor was completely resected, and postsurgical pathology demonstrated pancreatoblastoma with neuroendocrine manifestations. This case showed the metabolic and biological features of pancreatoblastoma on the 18F-FDG and 68Ga-DOTATATE PET/MR.
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Affiliation(s)
| | - Jing Xie
- Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yu Pan
- From the Departments of Nuclear Medicine
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Clinical Utility of 18F-FDG PET in Neuroendocrine Tumors Prior to Peptide Receptor Radionuclide Therapy: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:cancers13081813. [PMID: 33920195 PMCID: PMC8069875 DOI: 10.3390/cancers13081813] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/05/2021] [Accepted: 04/08/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Functional imaging with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has evolved into a major clinical tool in cancer diagnosis and management for many malignancies in diverse clinical settings, providing valuable information on tumor behavior and aggressiveness. In the field of neuroendocrine tumors (NETs), recent advances in molecular imaging and targeted treatments with novel theranostic agents favor a more patient-tailored approach. Although peptide receptor radionuclide therapy (PRRT) has recently become an established therapy for progressive NETs, the role of 18F-FDG PET prior to PRRT in patients with NETs of different origins and grades remains to be determined. Herein, we provide a comprehensive summary of available evidence in contemporary literature by means of a systematic review and meta-analysis, demonstrating that dual-functional imaging with 68Ga-DOTA-peptides and 18F-FDG prior to PRRT appears to be a useful tool in NET management by delineating tumor somatostatin receptor expression and glycolytic metabolic activity, and predicting tumor response and survival outcomes. Abstract The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27–10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48–4.04 and HR:2.25; 95% CIs:1.55–3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.
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Yadav D, Kumar R. Critical Role of 2-[18F]-fluoro-2-deoxy-glucose in Hormonally Active Malignancies. PET Clin 2021; 16:177-189. [PMID: 33648663 DOI: 10.1016/j.cpet.2020.12.007] [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] [Indexed: 12/11/2022]
Abstract
2-[18F]-fluoro-2-deoxyglucose (FDG) is the most commonly used radiotracer and provides valuable information about glucose metabolism. With the advent of newer receptor-based tracers in the management of hormonally active malignancies, the focus has been shifted from FDG. These tracers might be more specific than FDG because they target specific hormone receptors. But because FDG is widely available, this review discusses what information still can be harnessed from this workhorse of molecular imaging. The personalized implementation of FDG imaging in undifferentiated malignancies will help in characterization of tumor and may aid in patient management.
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Affiliation(s)
- Divya Yadav
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Rakesh Kumar
- Diagnostic Nuclear Medicine Division, Department of Nuclear Medicine, AIIMS, Ansari nagar, New Delhi 110029, India.
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Dual Tracer 68Ga-DOTATOC and 18F-FDG PET Improve Preoperative Evaluation of Aggressiveness in Resectable Pancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2021; 11:diagnostics11020192. [PMID: 33525712 PMCID: PMC7912034 DOI: 10.3390/diagnostics11020192] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 01/18/2021] [Accepted: 01/23/2021] [Indexed: 01/06/2023] Open
Abstract
PURPOSE To define an imaging risk profile in a population of patients affected by Pancreatic neuroendocrine neoplasms (PanNENs) candidates to surgery, by assessing the predictive role of 68Ga-DOTATOC and 18F-FDG PET/CT and PET/MR derived parameters in risk stratification, particularly regarding histological features of aggressive behaviour. PATIENTS AND METHODS Retrospective study including 83 patients (53 males, 30 females; median age: 60 years, interquartile range 52-66.5), who underwent to 68Ga-DOTATOC (PET/CT: n = 77; PET/MR: n = 6) and, 68/83 patients, also to 18F-FDG PET (PET/CT: n = 65; PET/MR: n = 3) before surgery for PanNEN between 2011 and 2019, with available histological and follow-up data. The PET scans were interpreted with both qualitative (positive vs. negative) and semiquantitative measurements as follows: maximum and mean standardized uptake value (SUVmax and SUVmean) for both 18F-FDG and 68Ga-DOTATOC scans, metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) for 18F-FDG scans and somatostatin receptor density (SRD) and total lesion somatostatin receptor density (TLSRD) for 68Ga-DOTATOC PET. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of several PET parameters in predicting tumour stage or characteristic. For each PET parameter, the optimal cut-off was derived. Logistic regression analysis was used to assess if the PET parameters, categorized with the optimal cut-off values, were able to predict significantly the corresponding tumour stage or characteristic. RESULTS Overall, 29 (35%) patients had G1, 49 (59%) a G2 and five (6%) had a G3 PanNEN. The median Ki-67 index was 4% (interquartile range: 1-8%). SRD and TLSRD significantly discriminated between pT3 or pT4 PanNEN versus pT1 or pT2, as well as 18F-FDG MTV and TLG. 68Ga-DOTATOC SUVmax was able to significantly predict the presence of distant metastases with a threshold of 51.27 (sensitivity and specificity of 85.7 and 68.1%, respectively). 18F-FDG MTV and TLG were predictors of angioinvasion. The cut-off threshold for MTV was 7.98 (sensitivity and specificity of 69.7 and 82.4%, respectively) (p = 0.0004) whereas the cut-off for TLG was 32.4 (sensitivity and specificity of 69.7% and 82.4%, respectively) (p = 0.0004). CONCLUSION Dual tracer 68Ga-DOTATOC and 18F-FDG PET scans provide relevant information regarding tumour behaviour and aggressiveness, implementing the diagnostic preoperative work-up.
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Zhou Z, Wang Z, Zhang B, Wu Y, Li G, Wang Z. Comparison of 68Ga-DOTANOC and 18F-FDG PET-CT Scans in the Evaluation of Primary Tumors and Lymph Node Metastasis in Patients With Rectal Neuroendocrine Tumors. Front Endocrinol (Lausanne) 2021; 12:727327. [PMID: 34539577 PMCID: PMC8440966 DOI: 10.3389/fendo.2021.727327] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/16/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Lymph node metastasis of rectal neuroendocrine tumors (RNETs) predicts poor prognosis. However, the assessment of lymph node metastasis remains a challenge. It has been reported that 68Ga-DOTANOC and 18F-FDG PET-CT scans could be employed in the work-up of rectal neuroendocrine tumors (RNETs). This study aimed to assess both tracers' ability to identify primary tumors and lymph node (LN) metastasis in RNETs. METHODS A total of 537 patients with RNETs were enrolled from January 2014 to January 2021. Both 68Ga-DOTANOC and 18F-FDG PET-CT scans were used to evaluate primary tumors and LN group metastasis. PET images were evaluated through visual and semiquantitative assessment. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of SUVmax of 68Ga-DOTANOC and 18F-FDG PET in predicting LN group metastasis. RESULTS Fifty-two patients with preoperative 68Ga-DOTANOC with 18F-FDG PET-CT scans underwent endoscopic biopsy or dissection of the primary tumor, while 11 patients underwent rectal surgery together with regional LN dissection. For primary tumors, 68Ga-DOTANOC had a sensitivity of 89.58% and a positive predictive value (PPV) of 95.56% through visual assessment, while 18F-FDG PET-CT showed 77.08% sensitivity and 97.37% PPV. For the prediction of LN group metastasis, 68Ga-DOTANOC PET-CT had 77.78% sensitivity and 91.67% specificity, while 18F-FDG PET-CT had 38.89% sensitivity and 100% specificity according to visual assessment. The area under the ROC curves (AUC) for 68Ga-DOTANOC PET/CT was 0.852 (95%CI:0.723-0.981) with an optimal SUVmax cut-off value of 2.25, while the AUC for 18F-FDG PET were 0.664 (95%CI:0.415-0.799) with an optimal SUVmax cut-off value of 1.05. CONCLUSIONS This study showed that 68Ga-DOTANOC PET-CT was a promising tool for detecting LN metastasis in RNETs with high sensitivity and specificity in visual assessment and semiquantitative assessment, which was better than 18F-FDG PET-CT.
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Affiliation(s)
- Zhihao Zhou
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhixiong Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bing Zhang
- Department of Nuclear Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yanzhang Wu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guanghua Li
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Zhao Wang, ; Guanghua Li,
| | - Zhao Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Zhao Wang, ; Guanghua Li,
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Mapelli P, Partelli S, Salgarello M, Doraku J, Pasetto S, Rancoita PMV, Muffatti F, Bettinardi V, Presotto L, Andreasi V, Gianolli L, Picchio M, Falconi M. Dual tracer 68Ga-DOTATOC and 18F-FDG PET/computed tomography radiomics in pancreatic neuroendocrine neoplasms: an endearing tool for preoperative risk assessment. Nucl Med Commun 2020; 41:896-905. [PMID: 32796478 DOI: 10.1097/mnm.0000000000001236] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM To explore the potentiality of radiomics analysis, performed on Ga-DOTATOC and fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) images, in predicting tumour aggressiveness and outcome in patients candidate to surgery for pancreatic neuroendocrine neoplasms (PanNENs). PATIENTS AND METHODS Retrospective study including 61 patients who underwent Ga-DOTATOC and F-FDG PET/CT before surgery for PanNEN. Semiquantitative variables [SUVmax and somatostatin receptor density (SRD) for Ga-DOTATOC PET; SUVmax and MTV for F-FDG PET] and texture features [intensity variability, size zone variability (SZV), zone percentage, entropy; homogeneity, dissimilarity and coefficient of variation (Co-V)] have been analysed to evaluate their possible role in predicting tumour characteristics. Principal component analysis (PCA) was firstly performed and then multiple regression analyses were performed by using the extracted principal components. RESULTS Regarding Ga-DOTATOC PET, SZV, entropy, intensity variability and SRD were predictive for tumour dimension. Regarding F-FDG PET, intensity variability, SZV, homogeneity, SUVmax and MTV were predictive for tumour dimension. Four principal components were extracted from PCA: PC1 correlated with all F-FDG variables, while PC2, PC3 and PC4 with Ga-DOTATOC variables. PC1 was the only significantly predicting angioinvasion (P = 0.0222); PC4 was the only one significantly predicting lymph nodal involvement (P = 0.0151). All principal components except PC4 significantly predicted tumour dimension (P <0.0001 for PC1, P = 0.0016 for PC2 and P < 0.0001 for PC3). Co-V from Ga-DOTATOC PET/CT was predictive of the outcome. CONCLUSION Specific texture features derived from preoperative Ga-DOTATOC and F-FDG PET/CT could noninvasively predict specific tumour characteristics and patients' outcome, delineating the potential role of dual tracer technique and texture analysis in the risk assessment of patients with PanNENs.
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Affiliation(s)
- Paola Mapelli
- Vita-Salute San Raffaele University
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute
| | - Stefano Partelli
- Vita-Salute San Raffaele University
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Milan
| | - Matteo Salgarello
- Department of Nuclear Medicine, IRCCS Sacro Cuore Don Calabria Hospital, Negrar
| | - Joniada Doraku
- Department of Nuclear Medicine, IRCCS Sacro Cuore Don Calabria Hospital, Negrar
| | - Stefano Pasetto
- Department of Nuclear Medicine, IRCCS Sacro Cuore Don Calabria Hospital, Negrar
| | - Paola M V Rancoita
- University Centre of Statistics in the Biomedical Sciences, Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Muffatti
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Milan
| | | | - Luca Presotto
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute
| | - Valentina Andreasi
- Vita-Salute San Raffaele University
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Milan
| | - Luigi Gianolli
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute
| | - Maria Picchio
- Vita-Salute San Raffaele University
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute
| | - Massimo Falconi
- Vita-Salute San Raffaele University
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Milan
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Pavel M, Öberg K, Falconi M, Krenning EP, Sundin A, Perren A, Berruti A. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020; 31:844-860. [PMID: 32272208 DOI: 10.1016/j.annonc.2020.03.304] [Citation(s) in RCA: 619] [Impact Index Per Article: 123.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 03/25/2020] [Accepted: 03/26/2020] [Indexed: 02/06/2023] Open
Affiliation(s)
- M Pavel
- Department of Medicine 1, University Hospital Erlangen, Erlangen, Germany
| | - K Öberg
- Department of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - M Falconi
- Department of Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - E P Krenning
- Cyclotron Rotterdam BV, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - A Sundin
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - A Perren
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - A Berruti
- Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology Unit, University of Brescia, ASST Spedali Civili, Brescia, Italy
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Tao L, Chen Y, Shi X, Yu G, Yin W, Huang Y. Expression of potential therapeutic target SSTR2a in primary and metastatic non-keratinizing nasopharyngeal carcinoma. Virchows Arch 2020; 477:573-579. [PMID: 32328798 DOI: 10.1007/s00428-020-02815-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 03/14/2020] [Accepted: 04/12/2020] [Indexed: 12/15/2022]
Abstract
Somatostatin receptor 2a (SSTR2a) is an important diagnostic and scintigraphic marker in several tumors, as well as a potential therapeutic target. However, the expression and clinicopathologic significance of SSTR2a in nasopharyngeal carcinoma (NPC) remain unknown. The expression of SSTR2a was retrospectively analyzed in a large series of NPC tissue samples (106 primary NPC samples, comprising 99 primary non-keratinizing NPC (NK-NPC) and 7 keratinizing NPC (K-NPC) samples, and 41 metastatic NPC samples) by immunohistochemistry, with 24 cases of normal nasopharyngeal mucosa tissues used as a control group. Normal epithelia in nasopharyngeal mucosa were negative for SSTR2a in all 24 cases. The expression of SSTR2a in primary NPC was correlated to the histological subtype. Most cases of primary NK-NPC showed expression of SSTR2a (93.9%, 93/99 cases). The percentage of SSTR2a-positive tumor cells ranged from 10 to 100%, while the intensity ranged from 2+ to 4+. None of the primary K-NPC samples showed SSTR2a expression (0/7, 100%). All cases of NPC showed negative expression of other neuroendocrine markers, including synaptophysin, chromogranin A, and CD56. Of all 41 cases of metastatic NK-NPC lesions, SSTR2a expression is concordant with that of the primary lesions, which shows statistical significance (p < 0.001). Our observations expand the spectrum of recognized SSTR2a-positive tumors and demonstrate for the first time that SSTR2a is frequently expressed in primary and metastatic NK-NPC, highlighting its potential as a scintigraphic and therapeutic target in this disease.
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Affiliation(s)
- Lili Tao
- Department of Pathology, Peking University Shenzhen Hospital, 1116 Lianhua Road, Futian District, Shenzhen, 518000, Guangdong, People's Republic of China
| | - Yaoli Chen
- Department of Pathology, Peking University Shenzhen Hospital, 1116 Lianhua Road, Futian District, Shenzhen, 518000, Guangdong, People's Republic of China
| | - Xiaoxin Shi
- Department of Pathology, Peking University Shenzhen Hospital, 1116 Lianhua Road, Futian District, Shenzhen, 518000, Guangdong, People's Republic of China
| | - Guangyin Yu
- Department of Pathology, Peking University Shenzhen Hospital, 1116 Lianhua Road, Futian District, Shenzhen, 518000, Guangdong, People's Republic of China
| | - Weihua Yin
- Department of Pathology, Peking University Shenzhen Hospital, 1116 Lianhua Road, Futian District, Shenzhen, 518000, Guangdong, People's Republic of China
| | - Yuhua Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China. .,Department of Pathology, Sun Yat-sen University Cancer Center, 651 Dong Feng East Road, Guangzhou, 510060, Guangdong, People's Republic of China.
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(Radio)Theranostic Patient Management in Oncology Exemplified by Neuroendocrine Neoplasms, Prostate Cancer, and Breast Cancer. Pharmaceuticals (Basel) 2020; 13:ph13030039. [PMID: 32151049 PMCID: PMC7151671 DOI: 10.3390/ph13030039] [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: 01/19/2020] [Revised: 03/01/2020] [Accepted: 03/03/2020] [Indexed: 12/18/2022] Open
Abstract
The role of nuclear medicine in the management of oncological patients has expanded during last two decades. The number of radiopharmaceuticals contributing to the realization of theranostics/radiotheranostics in the context of personalized medicine is increasing. This review is focused on the examples of targeted (radio)pharmaceuticals for the imaging and therapy of neuroendocrine neoplasms (NENs), prostate cancer, and breast cancer. These examples strongly demonstrate the tendency of nuclear medicine development towards personalized medicine.
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Duan H, Baratto L, Iagaru A. The Role of PET/CT in the Imaging of Pancreatic Neoplasms. Semin Ultrasound CT MR 2019; 40:500-508. [PMID: 31806148 DOI: 10.1053/j.sult.2019.04.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Pancreas cancer is a complex disease and its prognosis is related to the origin of the tumor cell as well as the stage of disease at the time of diagnosis. Pancreatic adenocarcinomas derive from the exocrine pancreas and are the fourth leading cause of cancer-related deaths in the United States, while well-differentiated pancreatic neuroendocrine tumors (pNETs) derived from the endocrine part of the pancreas are rare and characterized by a slow growth and good life expectancy. Surgery is the only curative treatment approach, and an accurate assessment of resectability is of paramount importance in order to avoid futile procedures. The role of molecular imaging with positron emission tomography and computed tomography ranges from indispensable for pNETs to controversial for certain scenarios in pancreatic adenocarcinomas. This review article aims to overview molecular pancreatic imaging.
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Affiliation(s)
- Heying Duan
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, CA
| | - Lucia Baratto
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, CA
| | - Andrei Iagaru
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, CA.
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Komek H, Ansal Balci T, Can C. Efficacy of Galium-68 DOTATATE PET/CT in the Detection of Metastasis Rate of Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors. ASIA OCEANIA JOURNAL OF NUCLEAR MEDICINE & BIOLOGY 2019; 7:141-148. [PMID: 31380453 PMCID: PMC6661313 DOI: 10.22038/aojnmb.2019.13348] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Objective(s): The aim of this study was to determine metastasis rate in patients with well-differentiated grade1 (G1) and grade 2 (G2) gastroenteropancreatic neuroendocrine tumors (GEP NETs) using the gallium-68 DOTATATE positron emission tomography/computed tomography (68Ga-DOTATATE PET/CT). This study was also targeted toward investigating the relationship of maximum standardized uptake value (SUVmax) with mitotic count, histological grade, and Ki-67 index. Methods: This retrospective study included 38 patients (i.e., 17 males and 21 females) with G1 or G2 GEP NETs who underwent 68Ga-DOTATATE PET/CT in Diyarbakir Gazi Yasargil training and research hospital between November 2014 and March 2018. The patients had at least one positive lesion that was approved by two nuclear medicine specialists with a minimum of 10 years of experience. Results: The median age of the patients was 50 years (age range: 27-80 years), and their mean age was 52±15 years. Out of 38 patients, 1 (2.6%), 2 (5.2%), 2 (5.2%), 3 (7.8%), 10 (28.5%), and 19 (50%) patients had primary hepatic, primary mesenteric, colon, duodenal, gastric, and pancreatic NETs, respectively. In addition, the liver metastasis, local lymph node invasions, distant lymph node metastasis, bone metastasis, peritoneal involvement, and lung metastasis were observed in 42%, 21%, 15.7%, 13%, 7.8%, and 5% of the cases, respectively. The SUVmax median values of G1 and G2 tumors were 9.45 (range: 4.2-43.6) and 34.9 (range: 4.1-103), respectively (P=0.003). The Ki-67 index showed a negative correlation with the SUVmax value of the liver metastases and the highest SUVmax value (P=0.001 and P=0.002, respectively). There was also a negative correlation between mitosis count and the highest SUVmax value (P=0.011). Conclusion: Based on the findings, although [68Ga]DOTATATE PET/CT is successfully used to diagnose primary GEP NETs and their metastases, the SUVmax value obtained from DOTATATE PET/CT showed a negative correlation with Ki-67 and mitotic count.
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Affiliation(s)
- Halil Komek
- Department of Nuclear Medicine, Gazi Yasargil Training and Research Hospital, Diyarbakir, Turkey
| | - Tansel Ansal Balci
- Department of Nuclear Medicine, Faculty of Medicine, Firat University, Elazig, Turkey
| | - Canan Can
- Department of Nuclear Medicine, Gazi Yasargil Training and Research Hospital, Diyarbakir, Turkey
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Carollo A, Papi S, Grana CM, Mansi L, Chinol M. State of the Art and Recent Developments of Radiopharmaceuticals for Pancreatic Neuroendocrine Tumors Imaging. Curr Radiopharm 2019; 12:107-125. [DOI: 10.2174/1874471012666190306104450] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 05/15/2018] [Accepted: 10/18/2018] [Indexed: 02/06/2023]
Abstract
Background:
Neuroendocrine Tumors (NETs) are relatively rare tumors, mainly originating
from the digestive system, that tend to grow slowly and are often diagnosed when metastasised. Surgery
is the sole curative option but is feasible only in a minority of patients. Among them, pancreatic neuroendocrine
tumors (pancreatic NETs or pNETs) account for less than 5% of all pancreatic tumors. Viable
therapeutic options include medical treatments such as biotherapies and more recently Peptide Receptor
Radionuclide Therapies (PRRT) with radiolabeled somatostatin analogues. Molecular imaging, with main
reference to PET/CT, has a major role in patients with pNETs.
Objective:
The overexpression of specific membrane receptors, as well as the ability of cells to take up
amine precursors in NET, have been exploited for the development of specific targeting imaging agents.
Methods:
SPECT/CT and PET/CT with specific isotopes such as [68Ga]-1,4,7,10-tetra-azacyclododecane-
N,N’,N’’,N’’’-tetra-acetic acid (DOTA)-somatostatin analogs, [18F]-FDG and [18F]-fluorodopa have been
clinically explored.
Results:
To overcome the limitations of SSTR imaging, interesting improvements are connected with the
availability of new radiotracers, activating with different mechanisms compared to somatostatin analogues,
such as glucagon-like peptide 1 receptor (GLP-1 R) agonists or antagonists.
Conclusion:
This paper shows an overview of the RPs used so far in the imaging of pNETs with insight
on potential new radiopharmaceuticals currently under clinical evaluation.
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Affiliation(s)
- Angela Carollo
- Division of Nuclear Medicine, European Institute of Oncology Via Ripamonti 435 20141 Milano, Italy
| | - Stefano Papi
- Division of Nuclear Medicine, European Institute of Oncology Via Ripamonti 435 20141 Milano, Italy
| | - Chiara M. Grana
- Division of Nuclear Medicine, European Institute of Oncology Via Ripamonti 435 20141 Milano, Italy
| | - Luigi Mansi
- Section Health and Development, Interuniversity Research Center for Sustainability (CIRPS), Napoli, Italy
| | - Marco Chinol
- Division of Nuclear Medicine, European Institute of Oncology Via Ripamonti 435 20141 Milano, Italy
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Carideo L, Prosperi D, Panzuto F, Magi L, Pratesi MS, Rinzivillo M, Annibale B, Signore A. Role of Combined [ 68Ga]Ga-DOTA-SST Analogues and [ 18F]FDG PET/CT in the Management of GEP-NENs: A Systematic Review. J Clin Med 2019; 8:E1032. [PMID: 31337043 PMCID: PMC6678236 DOI: 10.3390/jcm8071032] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 07/04/2019] [Accepted: 07/08/2019] [Indexed: 02/06/2023] Open
Abstract
Gastro-entero-pancreatic neuroendocrine neoplasia (GEP-NENs) are rare tumors, but their frequency is increasing. Neuroendocrine tumors normally express somatostatin (SST) receptors (SSTR) on cell surface, especially G1 and G2 stage tumors, but they can show a dedifferentiation in their clinical history as they become more aggressive. Somatostatin receptor imaging has previously been performed with a gamma camera using [111In]In or [99mTc]Tc-labelled compounds, while [68Ga]Ga-labelled compounds and PET/CT imaging has recently become the gold standard for the diagnosis and management of these tumors. Moreover, in the last few years 18F-fluorodeoxyglucose ([18F]FDG) PET/CT has emerged as an important tool to define tumor aggressiveness and give relevant prognostic information, particularly when coupled with [68Ga]Ga-labelled SST analogues PET/CT. This review focuses on the importance of combined imaging with [68Ga]Ga-labelled SST analogues and [18F]FDG for the management of GEP-NENs.
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Affiliation(s)
- Luciano Carideo
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Daniela Prosperi
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy.
| | - Francesco Panzuto
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Ludovica Magi
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Maria Sole Pratesi
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Bruno Annibale
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Alberto Signore
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
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Muffatti F, Partelli S, Cirocchi R, Andreasi V, Mapelli P, Picchio M, Gianolli L, Falconi M. Combined 68Ga-DOTA-peptides and 18F-FDG PET in the diagnostic work-up of neuroendocrine neoplasms (NEN). Clin Transl Imaging 2019. [DOI: 10.1007/s40336-019-00328-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Giovannini E, Giovacchini G, Borsò E, Lazzeri P, Riondato M, Leoncini R, Duce V, Ciarmiello A. [68Ga]-Dota Peptide PET/CT in Neuroendocrine Tumors: Main Clinical Applications. Curr Radiopharm 2019; 12:11-22. [PMID: 30539709 DOI: 10.2174/1874471012666181212101244] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/28/2018] [Accepted: 11/29/2018] [Indexed: 12/14/2022]
Abstract
Objective:
Neuroendocrine Neoplasms (NENs) are generally defined as rare and heterogeneous
tumors. The gastrointestinal system is the most frequent site of NENs localization, however they
can be found in other anatomical regions, such as pancreas, lungs, ovaries, thyroid, pituitary, and adrenal
glands. Neuroendocrine neoplasms have significant clinical manifestations depending on the
production of active peptide.
Methods:
Imaging modalities play a fundamental role in initial diagnosis as well as in staging and
treatment monitoring of NENs, in particular they vastly enhance the understanding of the physiopathology
and diagnosis of NENs through the use of somatostatin analogue tracers labeled with appropriate
radioisotopes. Additionally, the use of somatostatin analogues provides the ability to in-vivo measure
the expression of somatostatin receptors on NEN cells, a process that might have important therapeutic
implications.
Results:
A large body of evidences showed improved accuracy of molecular imaging based on PET/CT
radiotracer with SST analogues (e.g. [68Ga]-DOTA peptide) for the detection of NEN lesions in comparison
to morphological imaging modalities. So far, the role of imaging technologies in assessing
treatment response is still under debate.
Conclusion:
This review offers the systems of classification and grading of NENs and summarizes the
more useful recommendations based on data recently published for the management of patients with
NENs, with special focus on the role of imaging modalities based on SST targeting with PET / CT
radiotracers.
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Affiliation(s)
| | | | - Elisa Borsò
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Patrizia Lazzeri
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Mattia Riondato
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Rossella Leoncini
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Valerio Duce
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Andrea Ciarmiello
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
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Tripathy S, Ballal S, Yadav MP, Joshi P, Bal C, Damle NA. Coexistence of Multiple Metastatic Lesions Showing Various Grades of Differentiation in a Single Patient with Neuroendocrine Tumor of Lung as Primary: A Combined Modality Approach of 68Ga-DOTANOC Positron Emission Tomography/Computed Tomography and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging. Indian J Nucl Med 2019; 34:260-262. [PMID: 31293318 PMCID: PMC6593945 DOI: 10.4103/ijnm.ijnm_161_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Neuroendocrine tumors (NETs) of gastrointestinal (GI) tract and lungs are a rare variety of tumors but given their indolent nature are quite prevalent. These tumors are mostly malignant in nature and are often diagnosed in advanced stages. GI tracts are the most common sites of NETs followed by lungs, thymus, and other less common sites being ovaries, testis, and hepatobiliary system. Nuclear medicine imaging modalities include 68Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) which is sensitive for low-grade NETs and 18F-fluorodeoxyglucose (FDG) PET/CT which is more valuable for high-grade NETs. However, intermediate-grade NETs are equally sensitive to both 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT.
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Affiliation(s)
- Sarthak Tripathy
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjana Ballal
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Madhav Prasad Yadav
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Prashant Joshi
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Chandrasekhar Bal
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
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Lee L, Ito T, Jensen RT. Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 2018; 18:837-860. [PMID: 29973077 PMCID: PMC6283410 DOI: 10.1080/14737140.2018.1496822] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Recently, there have been a number of advances in imaging pancreatic neuroendocrine tumors (panNETs), as well as other neuroendocrine tumors (NETs), which have had a profound effect on the management and treatment of these patients, but in some cases are also associated with controversies. Areas covered: These advances are the result of numerous studies attempting to better define the roles of both cross-sectional imaging, endoscopic ultrasound, with or without fine-needle aspiration, and molecular imaging in both sporadic and inherited panNET syndromes; the increased attempt to develop imaging parameters that correlate with tumor classification or have prognostic value; the rapidly increasing use of molecular imaging in these tumors and the attempt to develop imaging parameters that correlate with treatment/outcome results. Each of these areas and the associated controversies are reviewed. Expert commentary: There have been numerous advances in all aspects of the imaging of panNETs, as well as other NETs, in the last few years. The advances are leading to expanded roles of imaging in the management of these patients and the results being seen in panNETs/GI-NETs with these newer techniques are already being used in more common tumors.
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Affiliation(s)
- Lingaku Lee
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
| | - Tetsuhide Ito
- c Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital International University of Health and Welfare 3-6-45 Momochihama , Sawara-Ku, Fukuoka , Japan
| | - Robert T Jensen
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
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Clinical and Prognostic Value of PET/CT Imaging with Combination of 68Ga-DOTATATE and 18F-FDG in Gastroenteropancreatic Neuroendocrine Neoplasms. CONTRAST MEDIA & MOLECULAR IMAGING 2018; 2018:2340389. [PMID: 29681780 PMCID: PMC5846381 DOI: 10.1155/2018/2340389] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 10/22/2017] [Accepted: 01/16/2018] [Indexed: 02/06/2023]
Abstract
Background To evaluate the clinical and prognostic value of PET/CT with combination of 68Ga-DOTATATE and 18F-FDG in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Method 83 patients of GEP-NENs who underwent 68Ga-DOTATATE and 18F-FDG PET/CT were enrolled between June 2013 and December 2016. Well-differentiated (WD) NETs are divided into group A (Ki-67 < 10%) and group B (Ki-67 ≥ 10%), and poorly differentiated (PD) NECs are defined as group C. The relationship between PET/CT results and clinicopathological characteristics was retrospectively investigated. Result For groups A/B/C, the sensitivities of 68Ga-DOTATATE and 18F-FDG were 78.8%/83.3%/37.5% and 52.0%/72.2%/100.0%. A negative correlation between Ki-67 and SUVmax of 68Ga-DOTATATE (R = −0.415; P ≤ 0.001) was observed, while a positive correlation was noted between Ki-67 and SUVmax of 18F-FDG (R = 0.683; P ≤ 0.001). 62.5% (5/8) of patients showed significantly more lesions in the bone if 68Ga-DOTATATE was used, and 22.7% (5/22) of patients showed more lymph node metastases if 18F-FDG was used. Conclusions The sensitivity of dual tracers was correlated with cell differentiation, and a correlation between Ki-67 and both SUVmax of PET-CTs could be observed. 68Ga-DOTATATE is suggested for WD-NET and 18F-FDG is probably suitable for patients with Ki-67 ≥ 10%.
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Kaewput C, Suppiah S, Vinjamuri S. Correlation between Standardized Uptake Value of 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and Pathological Classification of Neuroendocrine Tumors. World J Nucl Med 2018; 17:34-40. [PMID: 29398963 PMCID: PMC5778712 DOI: 10.4103/wjnm.wjnm_16_17] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
The aim of our study was to correlate tumor uptake of 68Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUVmax) and averaged SUV SUVmean of “main tumor lesions” were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 <2, intermediate grade: Ki-67 3–20, and high grade: Ki-67 >20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUVmax of tumor and Ki-67 index (r = −0.241) and negatively poor agreement between SUVmean of tumor and Ki-67 index (r = −0.094). SUVmax of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUVmean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUVmax and SUVmean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68Ga-DOTA-NOC may be associated with aggressive behavior and may, therefore, result in poor prognosis.
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Affiliation(s)
- Chalermrat Kaewput
- Department of Radiology, Division of Nuclear Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Subapriya Suppiah
- Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia, Selangor, Malaysia
| | - Sobhan Vinjamuri
- Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, UK
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Tirosh A, Kebebew E. The utility of 68Ga-DOTATATE positron-emission tomography/computed tomography in the diagnosis, management, follow-up and prognosis of neuroendocrine tumors. Future Oncol 2018; 14:111-122. [PMID: 29072093 PMCID: PMC5967363 DOI: 10.2217/fon-2017-0393] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 10/06/2017] [Indexed: 02/08/2023] Open
Abstract
Neuroendocrine tumors (NETs) are rare neoplasms that emerge mainly from the GI tract, pancreas and respiratory tract. The incidence of NETs has increased more than sixfold in the last decades. NETs typically express somatostatin receptors on their cell surface, which can be targeted by 'cold' somatostatin analogs for therapy or by 'hot' radiolabeled somatostatin analogs for tumor localization and treatment. 68-Gallium-DOTA peptides (DOTATATE, DOTATOC, DOTANOC) positron emission tomography/computed tomography is a highly accurate imaging modality for NETs that has been found to be more sensitive for NET detection than other imaging modalities. In the current review, we will discuss the clinical utility of 68-Gallium-DOTATATE positron emission tomography/computed tomography for the diagnosis and management of patients with NETs.
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Affiliation(s)
- Amit Tirosh
- Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Electron Kebebew
- Sackler Faculty of Medicine, Tel Aviv University, Israel
- Department of Surgery, The George Washington University School of Medicine & Health Sciences, Washington DC, USA
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Ruhlmann V, Poeppel TD, Veit J, Nagarajah J, Umutlu L, Hoffmann TK, Bockisch A, Herrmann K, Sauerwein W. Diagnostic accuracy of 18F-FDG PET/CT and MR imaging in patients with adenoid cystic carcinoma. BMC Cancer 2017; 17:887. [PMID: 29273015 PMCID: PMC5741915 DOI: 10.1186/s12885-017-3890-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 12/08/2017] [Indexed: 11/15/2022] Open
Abstract
Background The aim of this study was to evaluate the value of 18F–FDG PET/CT (PET/CT) and MRI for local and/or whole-body restaging of adenoid cystic carcinoma of the head and neck (ACC). Methods Thirty-six patients with ACC underwent conventional MRI of the head and neck and a whole-body PET/CT and were analysed with regards to detection of a local tumor recurrence, lymph node or distant metastases. A consensus interpretation of all available imaging data was used as reference standard. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were calculated for MRI and PET/CT. Results The sensitivity of PET/CT and MRI was 96% (89%), specificity 89% (89%), PPV 96% (96%), NPV 89% (73%) and accuracy 94% (89%) for detection of local tumors. Additionally, PET/CT revealed lymph node metastases in one patient and distant metastases in 9/36 patients. In three patients secondary primaries were found. Conclusions Whole-body PET/CT in addition to MRI of the head and neck improves detection of local tumour and metastastic spread in ACC.
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Affiliation(s)
- Verena Ruhlmann
- Department of Nuclear Medicine, University Duisburg-Essen, Medical Faculty, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
| | - Thorsten D Poeppel
- Department of Nuclear Medicine, University Duisburg-Essen, Medical Faculty, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Johannes Veit
- Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital Ulm, Frauensteige 12, 89070, Ulm, Germany
| | - James Nagarajah
- Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6525, GA, Nijmegen, the Netherlands
| | - Lale Umutlu
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Duisburg-Essen, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Thomas K Hoffmann
- Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital Ulm, Frauensteige 12, 89070, Ulm, Germany
| | - Andreas Bockisch
- Department of Nuclear Medicine, University Duisburg-Essen, Medical Faculty, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Ken Herrmann
- Department of Nuclear Medicine, University Duisburg-Essen, Medical Faculty, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Wolfgang Sauerwein
- Department of Radiation Oncology, University Duisburg-Essen, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany
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Kasajima A, Papotti M, Ito W, Brizzi MP, La Salvia A, Rapa I, Tachibana T, Yazdani S, Sasano H, Volante M. High interlaboratory and interobserver agreement of somatostatin receptor immunohistochemical determination and correlation with response to somatostatin analogs. Hum Pathol 2017; 72:144-152. [PMID: 29180250 DOI: 10.1016/j.humpath.2017.11.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 11/13/2017] [Accepted: 11/17/2017] [Indexed: 01/12/2023]
Abstract
Monoclonal antibodies to somatostatin receptors 2A (SSTR2A, UMB-1) and 5 (SSTR5, UMB-4) were reported to be highly reliable for immunohistochemical detection of these receptors in neuroendocrine neoplasms. However, the standardization of either the immunohistochemical procedure and the methods of evaluation has yet to be established. Fifty-two tissues from 38 patients with neuroendocrine neoplasm were retrieved from 2 institutions in Italy and Japan. The tissues were immunostained using 3 staining methodologies: 1 automated and 2 manual protocols from the Italian and Japanese institutions. The slides were independently evaluated by 3 observers (2 experienced pathologists and 1 medical student) using 3 scoring systems (Volante-Score, HER2-Score, and H-Score). The scores obtained from the staining methods were highly correlated with each other (r>0.85, P<.0001). Especially, the Volante- and HER2-Scores were highly concordant (r≥0.95, P≤.0001). Very high interobserver agreement was obtained irrespective of the method used and the experience of the evaluator, with the best concordance obtained by experienced pathologists evaluating automated system-stained slides (SSTR2A, r>0.97; SSTR5, r>0.96). HER2- and H-Scores were reliable to represent the characteristics of the patients. SSTR2A expression evaluated by the HER2-Score was significantly associated with clinical efficacy to somatostatin analogs (P=.04). SSTRs determination is an easily standardizable tool in different laboratories and is highly reproducible irrespective of the method of evaluation used. Given the positive association with clinical efficacy to somatostatin analogs, as well as the simple and widespread use, HER2-Score can be proposed as a standard evaluation procedure of SSTR2A and SSTR5 expression in neuroendocrine neoplasms.
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Affiliation(s)
- Atsuko Kasajima
- Department of Pathology, Tohoku University Graduate School of Medicine, 980-8574 Sendai, Japan; Department of Pathology, Technical University Munich, 81675 Munich, Germany.
| | - Mauro Papotti
- Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043 Turin, Italy; Città della Salute Hospital, Orbassano, 10126 Turin, Italy.
| | - Wataru Ito
- Department of Pathology, Tohoku University Graduate School of Medicine, 980-8574 Sendai, Japan.
| | - Maria Pia Brizzi
- Oncology Unit, San Luigi Hospital, Orbassano, 10043 Turin, Italy.
| | - Anna La Salvia
- Oncology Unit, San Luigi Hospital, Orbassano, 10043 Turin, Italy.
| | - Ida Rapa
- Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043 Turin, Italy.
| | - Tomoyoshi Tachibana
- Department of Pathology, Tohoku University Graduate School of Medicine, 980-8574 Sendai, Japan.
| | - Samaneh Yazdani
- Department of Pathology, Tohoku University Graduate School of Medicine, 980-8574 Sendai, Japan.
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, 980-8574 Sendai, Japan.
| | - Marco Volante
- Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043 Turin, Italy.
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Combined imaging with 68Ga-DOTA-TATE and 18F-FDG PET/CT on the basis of volumetric parameters in neuroendocrine tumors. Nucl Med Commun 2017; 37:874-81. [PMID: 27096719 DOI: 10.1097/mnm.0000000000000522] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
AIM To assess the additional contribution of the combined imaging approach with Ga-DOTA-TATE and fluorine-18 fluorodeoxyglucose (F-FDG) on the basis of volumetric parameters in neuroendocrine tumors (NETs). MATERIALS AND METHODS Forty-one patients with NET (19 women, 22 men; age range: 30-79 years; mean age: 56.7±12.3 years) underwent Ga DOTA-TATE and F-FDG PET/computed tomography (CT) imaging. Within the drawn regions of interest, in addition to evaluating the maximum and mean standardized uptake values (SUVmax and SUVmean), the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in F-FDG PET/CT imaging, and the somatostatin receptor density and total lesion somatostatin receptor expression (TLSRE) in Ga somatostatin receptor imaging (SRI) were measured. The patients were graded on the basis of the proliferation index: well (G1; Ki-67 ≤2), moderately (G2; Ki-67=3-20), and poorly (G3; Ki-67>20) differentiated groups. RESULTS Of the 41 NET patients, 22, 14, and five were in the G1 (53.7%), G2 (34.1%), and G3 (12.2%) groups, respectively. Liver metastases had significantly higher TLSRE values than the TLG values. Ki-67 levels showed a positive correlation with the primary tumor MTV and TLG values. Cg-A levels had a positive correlation with the volumetric parameters of the whole-body tumor burden (P<0.001). CONCLUSION Ga SRI and F-FDG PET/CT provide complementary information on treatment protocol and response assessment. While assessing the prognosis and tumor aggressiveness, lesions and whole-body tumor burdens can be calculated on the basis of volumetric parameters by F-FDG PET/CT using MTV and TLG, and by Ga SRI using somatostatin receptor density and TLSRE.
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Ito T, Jensen RT. Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management. Curr Opin Endocrinol Diabetes Obes 2017; 24:15-24. [PMID: 27875420 PMCID: PMC5195891 DOI: 10.1097/med.0000000000000300] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW The purpose is to review recent advances in molecular imaging of neuroendocrine tumors (NETs), discuss unresolved issues, and review how these advances are affecting clinical management. RECENT FINDINGS Molecular imaging of NETs underwent a number of important changes in the last few years, leading to some controversies, unresolved issues, and significant changes in clinical management. The most recent changes are reviewed in this article. Particularly important is the rapid replacement in somatostatin receptor scintigraphy of In-diethylenetriamine penta-acetic acid-single-photon emission computed tomography/computed tomography (CT) by Ga-fluorodopa(F-D)PA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptide-PET/CT imaging, which is now approved in many countries including the USA. Numerous studies in many different types of NETs demonstrate the greater sensitivity of Ga-DOTA-peptide PET/CT, its high specificity, and its impact on management. Other important developments in somatostatin receptor scintigraphy/molecular imaging include demonstrating the prognostic value of both Ga-DOTA-peptide PET/CT and F-fluoro-deoxyglucose PET/CT; how their use can be complementary; comparing the sensitivities and usefulness of Ga-DOTA-peptide PET/CT and F-FDOPA PET/CT; introducing new linkers and radiolabeled ligands such as Cu-DOTA-peptides with a long half-life, enhancing utility; and the introduction of somatostatin receptor antagonists which show enhanced uptake by NETs. In addition, novel ligands which interact with other receptors (GLP-1, bombesin, cholecystokinin, gastric inhibitory polpeptide, integrin, chemokines) are described, which show promise in the imaging of both NETs and other tumors. SUMMARY Molecular imaging is now required for all aspects of the management of patients with NETs. Its results are essential not only for the proper diagnostic management of the patient, but also for assessing whether the patient is a candidate for peptide receptor radionuclide therapy with Lu and also for providing prognostic value.
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Affiliation(s)
- Tetsuhide Ito
- aDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan bDigestive Diseases Branch, NIDDK, NIH, Bethesda, Maryland, USA
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Cingarlini S, Ortolani S, Salgarello M, Butturini G, Malpaga A, Malfatti V, DʼOnofrio M, Davì MV, Vallerio P, Ruzzenente A, Capelli P, Citton E, Grego E, Trentin C, De Robertis R, Scarpa A, Bassi C, Tortora G. Role of Combined 68Ga-DOTATOC and 18F-FDG Positron Emission Tomography/Computed Tomography in the Diagnostic Workup of Pancreas Neuroendocrine Tumors: Implications for Managing Surgical Decisions. Pancreas 2017; 46:42-47. [PMID: 27906872 DOI: 10.1097/mpa.0000000000000745] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Ga-DOTATOC (Ga) positron emission tomography (PET)/computed tomography (CT) is recommended in the workup of pancreas neuroendocrine tumors (PanNETs); evidence suggests that F-FDG (F) PET/CT can also provide prognostic information. Aims of this study were to assess the role of combined Ga- and F-PET/CT in the evaluation of grade (G) 1-2 PanNETs and to test the correlation between F-PET/CT positivity and tumor grade. METHODS Preoperative Ga- and F-PET/CT of 35 patients with surgically resected G1-2 PanNETs were evaluated. For grading, the 2010 World Health Organization Classification was used; an ancillary analysis with Ki67 cutoffs at 5% to 20% was conducted. Correlation between F-PET/CT positivity (SUVmax > 3.5) and grade was assessed. RESULTS Of 35 PanNETs, 28.6% and 71.4% were G1 and G2 as per World Health Organization. Ga-PET/CT showed high sensitivity (94.3%) in detecting G1-2 PanNETs. F-PET/CT was positive in 20% and 76% G1 and G2 tumors (P = 0.002). F-PET/CT identified G2 PanNETs with high positive predictive value (PPV, 90.5%). F-PET/CT correlated with tumor grade also in the ancillary analysis (P = 0.009). CONCLUSIONS The high sensitivity of Ga-PET/CT in NET detection is known. The high PPV of F-PET/CT in the identification of G2 forms suggests its potential role in PanNETs prognostication and risk stratification.
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Affiliation(s)
- Sara Cingarlini
- From the *Department of Oncology, Comprehensive Cancer Center, G.B. Rossi University Hospital of Verona; †Department of Nuclear Medicine, Sacro Cuore Don Calabria Hospital, Negrar; ‡Hepato-Biliary and Pancreas Unit, Pederzoli Hospital, Peschiera; Departments of §Pancreatic Surgery, ∥Radiology, ¶Internal Medicine, #Hepatobiliary Surgery, and **Pathology, Comprehensive Cancer Center, G.B. Rossi University Hospital of Verona, Verona, Italy
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Ronot M, Clift AK, Vilgrain V, Frilling A. Functional imaging in liver tumours. J Hepatol 2016; 65:1017-1030. [PMID: 27395013 DOI: 10.1016/j.jhep.2016.06.024] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Revised: 06/20/2016] [Accepted: 06/20/2016] [Indexed: 02/08/2023]
Abstract
Functional imaging encompasses techniques capable of assessing physiological parameters of tissues, and offers useful clinical information in addition to that obtained from morphological imaging. Such techniques may include magnetic resonance imaging with diffusion-weighted sequences or hepatobiliary contrast agents, perfusion imaging, or molecular imaging with radiolabelled tracers. The liver is of major importance in oncological practice; not only is hepatocellular carcinoma one of the malignancies with steadily rising incidence worldwide, but hepatic metastases are regularly observed with a range of solid neoplasms. Within the realm of hepatic oncology, different functional imaging modalities may occupy pivotal roles in lesion characterisation, treatment selection and follow-up, depending on tumour size and type. In this review, we characterise the major forms of functional imaging, discuss their current application to the management of patients with common primary and secondary liver tumours, and anticipate future developments within this field.
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Affiliation(s)
- Maxime Ronot
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM U1149, Centre de recherche biomédicale Bichat-Beaujon, CRB3, Paris, France
| | | | - Valérie Vilgrain
- Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM U1149, Centre de recherche biomédicale Bichat-Beaujon, CRB3, Paris, France.
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, UK
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Abstract
Neuroendocrine tumors (NETs) are rare heterogeneous neoplasm of variable aggressiveness. A 55-year-old woman underwent Ga-DOTANOC PET-CT for suspected NET, which revealed DOTANOC-avid soft tissue mass in the second part of the duodenum with multiple hepatic metastases. Another non-DOTANOC-avid abdominal mass and hypodense lesion in segment VI of the liver were noted. For further evaluation, FDG PET-CT was performed, which revealed increased uptake in the abdominal mass and lesion in segment VI of the liver. Biopsy from the previously mentioned lesions revealed poorly differentiated high-grade NET.
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Panagiotidis E, Alshammari A, Michopoulou S, Skoura E, Naik K, Maragkoudakis E, Mohmaduvesh M, Al-Harbi M, Belda M, Caplin ME, Toumpanakis C, Bomanji J. Comparison of the Impact of 68Ga-DOTATATE and 18F-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors. J Nucl Med 2016; 58:91-96. [DOI: 10.2967/jnumed.116.178095] [Citation(s) in RCA: 118] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 06/30/2016] [Indexed: 12/20/2022] Open
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Berardi R, Torniai M, Savini A, Rinaldi S, Cascinu S. Gastro-entero-pancreatic neuroendocrine tumors: Is now time for a new approach? World J Clin Oncol 2016; 7:131-134. [PMID: 27081635 PMCID: PMC4826958 DOI: 10.5306/wjco.v7.i2.131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/20/2015] [Accepted: 01/22/2016] [Indexed: 02/06/2023] Open
Abstract
Gastro-entero-pancreatic tumors (GEP-NETs) are rare neoplasms often characterized by an overexpression of somatostatin receptors. Thus, radiolabeled somatostatin analogues have showed an increasing relevance both in diagnosis and treatment, especially in low- and intermediate-differentiated GEP-NETs. These evidences have led to a growing development of new functional imaging techniques as 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) proved useful in the management of these neoplasms. However these tumors have a heterogeneous behavior also modifying their aggressiveness through time. Therefore sometimes 18F-fluorodeoxyglucose PET/CT appears to be more appropriate to obtain a better assessment of the disease. According to these considerations, the combination of different functional imaging techniques should be considered in the management of GEP-NETs patients allowing clinicians to choose the tailored therapeutic approach among available options.
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Beiderwellen K, Sabet A, Lauenstein TC, Lahner H, Poeppel TD. Neuroendokrine Neoplasien des Pankreas. Radiologe 2016; 56:348-54. [PMID: 27003413 DOI: 10.1007/s00117-016-0094-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Sharma P, Arora S, Dhull VS, Naswa N, Kumar R, Ammini AC, Bal C. Evaluation of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of pancreatic neuroendocrine tumors. ACTA ACUST UNITED AC 2015; 40:299-309. [PMID: 25134801 DOI: 10.1007/s00261-014-0219-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
PURPOSE To evaluate the diagnostic accuracy of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of pancreatic neuroendocrine tumors (NETs). METHODS Data of 141 (mean age 46.2 ± 15.2 years) patients who underwent 178 (68)Ga-DOTANOC PET/CT studies for diagnosis/staging (n = 88) and restaging (n = 90) of pancreatic NET were retrospectively analyzed. PET/CT results were compared to conventional imaging (CIM) when available (n = 86). Histopathology and/or clinical/imaging follow-up (minimum 6 months) were used as reference standard. RESULTS The overall sensitivity, specificity, and accuracy of (68)Ga-DOTANOC PET/CT were 85.7%, 79.1%, and 84.8%. The corresponding values were 73%, 50%, and 70.4% for diagnosis/staging groups and 98.6%, 100%, and 98.8% for restaging groups. The accuracy was significantly higher for restaging as compared to diagnosis/staging (P < 0.0001) and in non-insulinoma tumors than insulinomas (P < 0.0001). The SUVmax of primary tumors was significantly higher than metastatic lesions overall (P = 0.001), as well as in diagnosis/staging (P = 0.041) and restaging (P = 0.0003) subgroups. When available, CIM was less specific than (68)Ga-DOTANOC PET/CT (P < 0.001) and showed fewer lesions. CONCLUSIONS (68)Ga-DOTANOC PET/CT is useful for diagnosis/staging and restaging of patients with pancreatic NET. It demonstrates more lesions compared to CIM and is more specific.
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Affiliation(s)
- Punit Sharma
- Department of Nuclear Medicine and PET/CT, Eastern Diagnostics India Ltd., Kolkata, India,
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Velikyan I. Continued rapid growth in68Ga applications: update 2013 to June 2014. J Labelled Comp Radiopharm 2015; 58:99-121. [PMID: 25689590 DOI: 10.1002/jlcr.3250] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 11/13/2014] [Accepted: 11/21/2014] [Indexed: 12/21/2022]
Affiliation(s)
- Irina Velikyan
- Preclinical PET Platform, Department of Medicinal Chemistry; Uppsala University; SE-75183 Uppsala Sweden
- Department of Radiology, Oncology and Radiation Science; Uppsala University; SE-75285 Uppsala Sweden
- PET-Centre, Centre for Medical Imaging; Uppsala University Hospital; SE-75185 Uppsala Sweden
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Has Simsek D, Kuyumcu S, Turkmen C, Sanlı Y, Aykan F, Unal S, Adalet I. Can complementary 68Ga-DOTATATE and 18F-FDG PET/CT establish the missing link between histopathology and therapeutic approach in gastroenteropancreatic neuroendocrine tumors? J Nucl Med 2014; 55:1811-7. [PMID: 25315243 DOI: 10.2967/jnumed.114.142224] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
UNLABELLED Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are indolent neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. Tumor size, existence of metastasis, and histopathologic classification remain incapable in terms of treatment decision and prognosis estimation. This study aimed to compare (68)Ga-DOTATATE and (18)F-FDG PET/CT in GEPNETs and to investigate the relation between the complementary PET/CT results and histopathologic findings in the management of therapy, particularly in intermediate-grade patients. METHODS The relation between complementary (68)Ga-DOTATATE and (18)F-FDG PET/CT results of 27 GEPNET patients (mean age, 56 y; age range, 33-79 y) and histopathologic findings was evaluated according to grade and localization using standardized maximum uptake values and Ki67 indices. Grade 2 (G2) patients were further evaluated in 2 groups as G2a (3%-9%) and G2b (10%-20%) according to Ki67 indices. RESULTS The sensitivity of (68)Ga-DOTATATE and (18)F-FDG PET/CT was 95% and 37%, respectively, and the positive predictive values were 93.8% and 36.2%, respectively. The sensitivity in detecting liver metastasis, lymph nodes, bone metastasis, and primary lesion was 95%, 95%, 90%, and 93% for (68)Ga-DOTATATE and 40%, 28%, 28%, and 75% for (18)F-FDG, respectively. Statistically significant differences were found between grades 1-2, 2a-2b, and 1-2b with respect to (68)Ga-DOTATATE PET/CT as well as between 1-2a and 1-2b with respect to (18)F-FDG PET/CT. However, no statistical differences were found between 1 and 2a (P > 0.05) for (68)Ga-DOTATATE and 2a and 2b (P = 0.484) for (18)F-FDG. The impact of the combined (18)F-FDG and (68)Ga-DOTATATE PET/CT on the therapeutic decision was 59%. CONCLUSION Combined (68)Ga-DOTATATE and (18)F-FDG PET/CT is helpful in the individual therapeutic approach of GEPNETs and can overcome the shortcomings of histopathologic grading especially in intermediate-grade GEPNETs.
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Affiliation(s)
- Duygu Has Simsek
- Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; and
| | - Serkan Kuyumcu
- Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; and
| | - Cuneyt Turkmen
- Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; and
| | - Yasemin Sanlı
- Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; and
| | - Faruk Aykan
- Department of Medical Oncology, Institution of Oncology, Istanbul University, Istanbul, Turkey
| | - Seher Unal
- Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; and
| | - Isik Adalet
- Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey; and
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Schillaci O. Can PET/CT Guide the Personalized Treatment of Patients with Gastroenteropancreatic Neuroendocrine Neoplasms? J Nucl Med 2014; 55:1757-8. [DOI: 10.2967/jnumed.114.147538] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
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Sharma P, Naswa N, Kc SS, Alvarado LA, Dwivedi AK, Yadav Y, Kumar R, Ammini AC, Bal C. Comparison of the prognostic values of 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor. Eur J Nucl Med Mol Imaging 2014; 41:2194-202. [PMID: 25030618 DOI: 10.1007/s00259-014-2850-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 06/27/2014] [Indexed: 12/17/2022]
Abstract
PURPOSE To determine the prognostic value of (68)Ga-DOTANOC PET/CT in patients with well-differentiated neuroendocrine tumor (NET), and to compare the prognostic value with that of (18)F-FDG PET/CT and other conventional clinicopathological prognostic factors. METHODS Data from 37 consecutive patients (age 46.6 ± 13.5 years, 51% men) with well-differentiated NET who underwent (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT were analyzed. All patients underwent a baseline visit with laboratory and radiological examinations. Clinical and imaging follow-up was performed in all patients. Progression-free survival (PFS) was measured from the date of the first PET/CT scan to the first documentation of progression of disease. RESULTS (68)Ga-DOTANOC PET/CT was positive in 37 of the 37 patients and (18)F-FDG PET/CT was positive in 21. During follow-up 10 patients (27%) showed progression of disease and 27 (73%) showed no progression (24 stable disease, 3 partial response). The median follow-up was 25 months (range 2 - 52 months). Among the variables evaluated none was significantly different between the progressive disease and nonprogressive disease groups, with only SUVmax on (68)Ga-DOTANOC PET/CT being borderline significant (P = 0.073). In the univariate analysis for PFS outcome, SUVmax on (68)Ga-DOTANOC PET/CT (HR 0.122, 95% CI 0.019 - 0.779; P = 0.026) and histopathological tumor grade (HR 4.238, 95% CI 1.058 - 16.976; P = 0.041) were found to be associated with PFS. Other factors including age, sex, primary site, Ki-67 index, TNM stage, (18)F-FDG PET/CT status (positive/negative), SUVmax on (18)F-FDG PET/CT and type of treatment were not significant. In multivariable analysis, only SUVmax on (68)Ga-DOTANOC PET/CT was found to be an independent positive predictor of PFS (HR 0.122, 95% CI 0.019 - 0.779; P = 0.026). CONCLUSION SUVmax measured on (68)Ga-DOTANOC PET/CT is an independent, positive prognostic factor in patients with well-differentiated NET and is superior to SUVmax on (18)F-FDG PET/CT and conventional clinicopathological factors for predicting PFS.
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Affiliation(s)
- Punit Sharma
- Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
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