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22 pages, 24661 KiB  
Review
Imaging of Liver Metastases from GEP-NETs: A Narrative Review
by Alessandro Posa, Enza Genco, Pierluigi Barbieri, Mario Ariano, Marcello Lippi, Alessandro Maresca and Roberto Iezzi
Onco 2025, 5(3), 36; https://doi.org/10.3390/onco5030036 - 17 Jul 2025
Viewed by 216
Abstract
Prompt and accurate identification of liver metastases from neuroendocrine tumors, arising from the gastrointestinal system and from the pancreas, through the means of both anatomical and functional diagnostic imaging techniques is mandatory. A patient’s prognosis and treatment planning are dependent on these diagnostic [...] Read more.
Prompt and accurate identification of liver metastases from neuroendocrine tumors, arising from the gastrointestinal system and from the pancreas, through the means of both anatomical and functional diagnostic imaging techniques is mandatory. A patient’s prognosis and treatment planning are dependent on these diagnostic procedures. The aim of this narrative review is to depict the common appearance of liver metastases, as well as to depict atypical imaging patterns. Moreover, this review will cover the differential diagnosis between liver metastases from neuroendocrine tumors and other primary and secondary malignant liver lesions, as well as benign liver lesions. Full article
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12 pages, 4529 KiB  
Article
Somatostatin Receptor Expression of Gastroenteropancreatic Neuroendocrine Tumors: A Comprehensive Analysis in the Era of Somatostatin Receptor PET Imaging
by Maria Grazia Maratta, Taymeyah Al-Toubah, Jaime Montilla-Soler, Eleonora Pelle, Mintallah Haider, Ghassan El-Haddad and Jonathan Strosberg
Cancers 2025, 17(12), 1937; https://doi.org/10.3390/cancers17121937 - 11 Jun 2025
Cited by 1 | Viewed by 593
Abstract
Background: There is limited data on somatostatin receptor (SSTR) expression of metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using modern imaging techniques and stratifying by primary site and tumor grade (G). Understanding patterns of SSTR expression and tumor heterogeneity is essential when determining the [...] Read more.
Background: There is limited data on somatostatin receptor (SSTR) expression of metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using modern imaging techniques and stratifying by primary site and tumor grade (G). Understanding patterns of SSTR expression and tumor heterogeneity is essential when determining the relevance of cold and radiolabeled somatostatin analog treatments. Methods: A single-institutional retrospective analysis of metastatic well-differentiated G1-3 GEP-NET patients who underwent Gallium-68 ([68Ga])-DOTATATE or Copper-64 ([64Cu])-DOTATATE positron emission tomography (PET) imaging from September 2016 to June 2024 was performed. Results: A total of 1192 patients were considered eligible for this study. Among them, 26 (2.2%) were completely negative on SSTR PET/computed tomography (CT), and 27 (2.3%) had weak uptake (less or equal to the normal liver). Up to 40 (3.4%) had heterogeneous SSTR expression on PET/CT: 26 (2.2%) displayed the coexistence of strongly avid lesions with the absence or near absence of SSTR uptake in measurable tumors (heterogeneous strong), while 14 (1.2%) had a combination of absent and weakly expressing SSTR tumors (heterogeneous low). An additional nine cases with prior homogeneous expression (0.8%) developed new SSTR-negative tumors along with disease progression, potentially indicating dedifferentiation. The absent or heterogeneous SSTR expression rates were greater in NET G3 than G1/G2 and in tumors originating outside the small bowel (midgut). Most NETs with absent or heterogeneous SSTR expression were fluorodeoxyglucose-F-18 ([18F]FDG)-avid. Conclusions: The large majority of metastatic GEP-NETs demonstrate strong and relatively uniform SSTR expression, but approximately 8% are SSTR-negative, weak or heterogeneous on PET/CT. Higher than average rates of absent/heterogeneous/weak SSTR expression occur in G3 NETs and lower rates among small intestine primaries. Full article
(This article belongs to the Special Issue Updates in Neuroendocrine Neoplasms)
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23 pages, 1894 KiB  
Review
From Seeing to Healing: The Clinical Potential of Radiotracers in Pediatric Neuro-Oncology
by Bojana Bogdanović and Christopher Montemagno
Cancers 2025, 17(12), 1905; https://doi.org/10.3390/cancers17121905 - 7 Jun 2025
Viewed by 756
Abstract
Pediatric central nervous system (CNS) tumors, including gliomas, medulloblastomas, and diffuse midline gliomas (previously diffuse intrinsic pontine gliomas), remain a major clinical challenge due to their complex biology, limited treatment effectiveness, and generally poor prognosis. Standard treatments are often aggressive and associated with [...] Read more.
Pediatric central nervous system (CNS) tumors, including gliomas, medulloblastomas, and diffuse midline gliomas (previously diffuse intrinsic pontine gliomas), remain a major clinical challenge due to their complex biology, limited treatment effectiveness, and generally poor prognosis. Standard treatments are often aggressive and associated with substantial toxicity, particularly in advanced stages. This review highlights recent developments in radiopharmaceuticals for molecular imaging and targeted radiotherapy. A comprehensive literature analysis was conducted, focusing on radiotracers with clinical relevance in pediatric neuro-oncology, including metabolic, peptide receptor-based, and antibody-based agents. Radiopharmaceuticals such as 18F-FLT, 64CuCl2, and 1-L-18F-FETrp have improved the ability to monitor tumor biology, proliferation, and treatment response, aiding in diagnosis at an early stage, assessment of tumor behavior, and detection of recurrence or progression. Additionally, peptide receptor-based radiotracers, such as 68Ga-DOTATATE and 177Lu-DOTATATE, are already used for both diagnostic purposes and targeted radiotherapy, particularly in neuroblastomas and gliomas. Antibody-based radiotracers like 131I-omburtamab, targeting B7-H3, are emerging as promising tools for addressing difficult-to-treat tumors such as diffuse midline glioma. Collectively, these advances provide new hope for children afflicted by these devastating malignancies, offering promising solutions for more specific and precise diagnosis and, additionally, for more effective, personalized, and less toxic tumor therapies. Full article
(This article belongs to the Special Issue Pediatric Brain Tumors: Symptoms, Diagnosis and Treatments)
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21 pages, 5367 KiB  
Case Report
History of an Insidious Case of Metastatic Insulinoma
by Katarzyna Antosz-Popiołek, Joanna Koga-Batko, Wojciech Suchecki, Małgorzata Stopa, Katarzyna Zawadzka, Łukasz Hajac, Marek Bolanowski and Aleksandra Jawiarczyk-Przybyłowska
J. Clin. Med. 2025, 14(12), 4028; https://doi.org/10.3390/jcm14124028 - 6 Jun 2025
Viewed by 716
Abstract
In this article, we present a case of a 49-year-old woman presenting with a recurrent metastatic neuroendocrine tumor. Background: Insulinomas are neuroendocrine tumors derived from beta cells of the pancreas that secrete insulin. Usually, they are benign tumors; however, metastatic insulinomas are [...] Read more.
In this article, we present a case of a 49-year-old woman presenting with a recurrent metastatic neuroendocrine tumor. Background: Insulinomas are neuroendocrine tumors derived from beta cells of the pancreas that secrete insulin. Usually, they are benign tumors; however, metastatic insulinomas are an extremely rare malignant form of these tumors, carrying a significantly worse prognosis. Case Presentation: A 49-year-old woman, a patient in the University Hospital in Wroclaw in the Department of Endocrinology, Diabetes and Isotope Therapy, first presented with abdominal pain in 2009, when ultrasound and further examination led to the diagnosis of a tumor in the pancreas (a solid pseudopapillary tumor of the pancreas—meta NET G2), and the patient underwent distal pancreatectomy with splenectomy. For ten years, she was under observation, and her symptoms, such as abdominal pain, nausea, weight loss, and general weakness, reappeared in 2019. Then, magnetic resonance imaging (MRI) showed a lesion in the liver, and further histopathology revealed neuroendocrine tumor (NET) metastasis to the liver. In 2022, the patient presented with loss of consciousness and convulsion, loss of weight, and hypoglycemia after meals. In April 2022, the daily glycemic profile was recorded and a 72 h fasting test was performed; however, their results excluded insulinoma. Positron emission tomography–computed tomography (PET-CT) with 18F-fluorodeoxyglucose (18F-FDG) and PET with gallium-68-DOTA-(Tyr3)-octreotate (68Ga-DOTA-TATE) showed a metastatic proliferative process in the liver. Persistent hypoglycemia led to another hospitalization in May 2022, and repeated tests allowed for the diagnosis of insulinoma. Treatment with somatostatin analogs and diazoxide was started. A CT scan in November 2022 and a PET scan in January 2023 showed new metastases to the liver, bones, and cervical lymph nodes, and it was decided to intensify the treatment. In May 2023, the patient was qualified for Lutathera treatment for insulinoma at the University Clinical Hospital in Poznań. In June 2023, another disturbing symptom was reported by the patient, a painful lump in the breast. During diagnostics, metastases with high proliferation markers were found in both breasts. Two months later, in August 2023, the patient received another dose of Lutathera. In October 2023, significant progression of liver lesions, metastases to bones of the spine, ribs, and pelvis, and periaortic and pelvic lymphadenopathy were found as well as elevated values of neuron-specific enolase and calcitonin. The patient was also referred to the Palliative Medicine Home Hospice. In consultation with the Lower Silesian Cancer Center, the decision was made to forgo further treatment with PRRT and initiate systemic chemotherapy. Despite the chosen treatment, the patient died on 27/DEC/2023. Conclusions: This case report can serve clinicians, as it presents a case of an extremely rare and insidious tumor, metastatic insulinoma. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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19 pages, 769 KiB  
Review
Meningioma: Novel Diagnostic and Therapeutic Approaches
by Carlen A. Yuen, Michelle Zheng, Max A. Saint-Germain and David O. Kamson
Biomedicines 2025, 13(3), 659; https://doi.org/10.3390/biomedicines13030659 - 7 Mar 2025
Cited by 2 | Viewed by 2378
Abstract
Background/Objectives: Meningiomas are the most common intracranial tumors. Surgery and radiation therapy are the cornerstones of treatment and no standard of care therapy exists for refractory meningiomas. This manuscript aims to provide a comprehensive review of novel diagnostic and therapeutic approaches against [...] Read more.
Background/Objectives: Meningiomas are the most common intracranial tumors. Surgery and radiation therapy are the cornerstones of treatment and no standard of care therapy exists for refractory meningiomas. This manuscript aims to provide a comprehensive review of novel diagnostic and therapeutic approaches against these tumors. Methods: A search for the existing literature on systemic therapies for meningiomas was performed on PubMed and a search for presently accruing clinical trials was performed on ClinicalTrials.gov. Results: Systemic treatments, including chemotherapy, somatostatin analogs, anti-hormone therapy, and anti-angiogenic therapy, have been extensively studied with marginal success. Targeted therapies are actively being studied for the treatment of meningiomas, including focal adhesion kinase (FAK), sonic hedgehog signaling pathway, phosphoinositide-3-kinase (PI3K), and cyclin-dependent kinases (CDK) inhibitors. These driver mutations are present only in a subset of meningiomas. In stark contrast, somatostatin receptor 2 (SSTR2) is ubiquitously expressed in meningiomas and was formerly targeted with somatostatin analogs with modest success. Theranostic SSTR2-targeting via [68Ga]DOTATATE for PET imaging and β-emitting [177Lu]DOTATATE for the treatment of meningiomas are currently under active investigation. Conclusions: A nuanced approach is needed for the treatment of refractory meningiomas. Targeted therapies show promise. Full article
(This article belongs to the Special Issue Meningioma: Novel Diagnostic and Therapeutic Approaches)
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8 pages, 1354 KiB  
Case Report
Autoimmune Pancreatitis Mimicking a Pancreatic Neuroendocrine Tumor: A Case Report with a Literature Review
by Marianna Franchina, Liliana Dell’Oro and Sara Massironi
Int. J. Mol. Sci. 2025, 26(4), 1536; https://doi.org/10.3390/ijms26041536 - 12 Feb 2025
Viewed by 1254
Abstract
Autoimmune pancreatitis (AIP) is a rare chronic pancreatitis subtype that often mimics pancreatic cancer due to the overlapping clinical and radiological features, posing significant diagnostic challenges. Similarly, distinguishing AIP from pancreatic neuroendocrine neoplasms (PanNENs), which present with nonspecific symptoms, adds complexity to clinical [...] Read more.
Autoimmune pancreatitis (AIP) is a rare chronic pancreatitis subtype that often mimics pancreatic cancer due to the overlapping clinical and radiological features, posing significant diagnostic challenges. Similarly, distinguishing AIP from pancreatic neuroendocrine neoplasms (PanNENs), which present with nonspecific symptoms, adds complexity to clinical evaluations. We present the case of a 46-year-old male with recurrent acute idiopathic pancreatitis. Abdominal computed tomography (CT) revealed a 25 mm hypodense mass in the pancreatic tail with mild arterial contrast enhancement. Magnetic resonance imaging (MRI) showed the mass to be hypointense on T2-weighted sequences, with no diffusion restriction and an enhancement pattern akin to normal pancreatic tissue. The endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) was inconclusive. Gallium-68 DOTATATE positron emission tomography–CT (Ga-68 DOTATATE PET-CT) showed an increased tracer uptake, leading to a distal pancreatectomy with a splenectomy. Histopathology demonstrated chronic sclerotic pancreatitis with inflammatory infiltrates. Elevated serum IgG4 levels confirmed the diagnosis of type 1 AIP Differentiating AIP from pancreatic malignancies, including PanNENs, is both critical and complex. This case highlights a misdiagnosis of PanNENs in a patient with focal AIP, where neuroendocrine hyperplasia and islet cell clusters within fibrotic areas mimicked PanNENs, even on Ga-68 PET-CT. The findings emphasize the potential for false positives with Ga-68 DOTATATE PET-CT and the importance of integrating clinical, radiological, and histological data for an accurate diagnosis. Full article
(This article belongs to the Special Issue Molecular Mechanisms Underlying Metastatic Potential in Cancer)
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14 pages, 8161 KiB  
Article
68Ga-DOTATATE PET/CT in the Initial Staging of Well-Differentiated Gastroenteropancreatic and Non-Gastroenteropancreatic Neuroendocrine Tumors: Results of a Prospective Registry
by Ur Metser, Roshini Kulanthaivelu, Julia Duder, Ricarda Hinzpeter, Simron Singh, Rebecca Wong, Sten Myrehaug, Daryl Gray, Patrick Veit-Haibach, Amit Singnurkar, Xuan Li and Shereen Ezzat
Cancers 2025, 17(3), 434; https://doi.org/10.3390/cancers17030434 - 27 Jan 2025
Viewed by 1294
Abstract
Background and Objectives: At diagnosis, the initial staging of well-differentiated neuroendocrine tumors (WD NETs) aids in treatment planning. The somatostatin receptor (SSTR)-PET has been recommended for staging of WD NETs although limited data are available on its impact on non-gastroeneteropancreatic (GEP) NETs. The [...] Read more.
Background and Objectives: At diagnosis, the initial staging of well-differentiated neuroendocrine tumors (WD NETs) aids in treatment planning. The somatostatin receptor (SSTR)-PET has been recommended for staging of WD NETs although limited data are available on its impact on non-gastroeneteropancreatic (GEP) NETs. The main purpose of this study was to compare the stage migration after the addition of SSTR-PET to the workup of patients at the initial staging of GEP NETs to those with non-GEP NETs, and its potential impact on patient management. Methods: This prospective study included patients with WD NETs at initial staging. Demographic data, results of conventional and SSTR-PET staging, and SUVmax were recorded. Three panels of experts assessed the potential impact of SSTR-PET to management. Results: There were 482 patients, including 376 with gastroenteropancreatic (GEP) NETs and 106 non-GEP NETs with a median SUVmax of 34.7 [Q1, Q3: 22.8, 59.1]) and 19.0 [Q1, Q3: 7.9, 39.8]), respectively; p < 0.001. The discordant M-stage was recorded in 111/473 patients (23.5%). PET suggested a higher stage in 78/369 GEP NETs (21.1%), including the detection of extrahepatic metastatic disease in 42/114 (36.8%) patients with liver metastases only on CI. For non-GEP NETs, PET suggested a higher stage in 10/104 (9.6%) and CI suggested a higher stage in 15/104 (14.4%), with CI detecting liver metastases more frequently. The potential impact to management for patients with discordant M-stage was scored as moderate to high between 57/101 (56.4%) and 79/101 (78.2%) of patients. Conclusions: One in five patients are upstaged following SSTR-PET, more frequently with GEP NETs than others. SSTR-PET identifies extrahepatic metastatic disease in >1/3 of patients with presumed liver-only metastases on CI. Stage migration following SSTR-PET may result in frequent moderate or significant management change. Full article
(This article belongs to the Special Issue Neuroendocrine Tumors: From Diagnosis to Therapy)
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11 pages, 7000 KiB  
Communication
SSTR2-Targeted Theranostics in Hepatocellular Carcinoma
by Majid Momeny, Solmaz AghaAmiri, Servando Hernandez Vargas, Belkacem Acidi, Sukhen C. Ghosh, Tyler M. Bateman, Jack T. Adams, Vahid Khalaj, Ahmed O. Kaseb, Hop S. Tran Cao and Ali Azhdarinia
Cancers 2025, 17(2), 162; https://doi.org/10.3390/cancers17020162 - 7 Jan 2025
Viewed by 1332
Abstract
Background: While the clinical use of radiolabeled somatostatin analogs is well established in neuroendocrine tumors, there is growing interest in expanding their application to other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the potential utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC). [...] Read more.
Background: While the clinical use of radiolabeled somatostatin analogs is well established in neuroendocrine tumors, there is growing interest in expanding their application to other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the potential utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC). Methods: SSTR2 expression in HCC cell lines and clinical samples was evaluated using qRT-PCR, Western blot analysis, and a public dataset. 67Ga-DOTATATE uptake was measured, 177Lu-DOTATATE cytotoxicity was assessed, and 68Ga-DOTATATE tumor targeting was evaluated in HCC animal models and a patient via PET/CT imaging. Results: SSTR2 expression was confirmed in HCC cell lines and clinical samples. Radioligand uptake studies demonstrated SSTR2-mediated 67Ga-DOTATATE uptake. 177Lu-DOTATATE treatment reduced cell proliferation and enhanced the anti-tumor efficacy of the multikinase inhibitor sorafenib. 68Ga-DOTATATE PET/CT scans successfully identified tumors in HCC animal models and spinal metastases in a patient with HCC. Conclusion: These findings provide evidence that SSTR2-based theranostics could have significant implications for the detection and treatment of HCC. Full article
(This article belongs to the Special Issue G Protein-Coupled Receptors in Cancer Progression)
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12 pages, 1727 KiB  
Systematic Review
The Efficacy of Positron Emission Tomography/Computed Tomography Scan (PET CT Scan) in the Diagnosis of Local Recurrence and Metastases in Surgical Patients with Medullary Thyroid Carcinoma: A Systematic Review and Meta-Analysis of the Last 5 Years (2020–2024)
by Konstantinos Papadopoulos, Ioannis Iakovou, Stylianos Mantalovas, Christoforos S. Kosmidis, Stiliani Laskou, Vasileios Alexandros Karakousis, Christina Sevva, Marios Dagher, Panagiota Roulia, Ismini Kountouri, Isaak Kesisoglou and Konstantinos Sapalidis
Cancers 2024, 16(24), 4236; https://doi.org/10.3390/cancers16244236 - 19 Dec 2024
Viewed by 1677
Abstract
Background/Objectives: Medullary thyroid carcinoma (MTC) is a highly aggressive tumor, as it is characterized by a high probability of local recurrence and distant metastases, even after surgical treatment. Early detection of disease recurrence is critical for improving long-term treatment outcomes and overall patient [...] Read more.
Background/Objectives: Medullary thyroid carcinoma (MTC) is a highly aggressive tumor, as it is characterized by a high probability of local recurrence and distant metastases, even after surgical treatment. Early detection of disease recurrence is critical for improving long-term treatment outcomes and overall patient survival. By comparing different radiopharmaceuticals, this analysis aimed to strengthen existing guidelines and help bridge the gap between the recommendations of the ESMO and the ATA, highlighting the importance of PET/CT scanning in the postoperative follow-up of patients with MTC. Methods: This research was carried out using three searchable databases, PubMed, ScienceDirect, and ResearchGate, resulting in 575 bibliographic studies up to the date of 20 June 2024. A meta-analysis of diagnostic accuracy was performed using the software Meta—DiSc, Version: 2.0 (Universidad Complutense, Barcelona, Spain), which led to aggregate assessments and the design of the SROC. Results: A quality assessment of the eligible studies was conducted, and the key findings were summarized. Conclusions: Regardless of methodology, PET/CT scanning exhibits high sensitivity and specificity values in the diagnosis of local recurrence and metastases in surgical patients with medullary thyroid carcinoma. Furthermore, based on a comparative analysis of18F-FDG and GA68-DOTATE, it appears that these misunderstood radiopharmaceuticals are particularly sensitive and reliable for highlighting MTC, and it was found that there were no statistical differences in terms of sensitivity and specificity. Therefore, these two modalities appear to be complementary in monitoring MTC patients. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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12 pages, 5288 KiB  
Article
Preclinical Study of a Dual-Target Molecular Probe Labeled with 68Ga Targeting SSTR2 and FAP
by Huanhuan Liu, Xiaojun Zhang, Yue Pan, Jingfeng Zhang, Hui Wen, Cong Zhang, Xiaodan Xu, Guangyu Ma, Ruimin Wang and Jinming Zhang
Pharmaceuticals 2024, 17(12), 1647; https://doi.org/10.3390/ph17121647 - 7 Dec 2024
Viewed by 1705
Abstract
Objective: Currently, 68Ga-labeled somatostatin analogs (SSAs) are the most commonly used imaging agents for patients with neuroendocrine tumors (NETs) in clinical practice, demonstrating good results in tumor diagnosis. For applications in peptide receptor radionuclide therapy (PRRT), targeted drugs should have high tumor [...] Read more.
Objective: Currently, 68Ga-labeled somatostatin analogs (SSAs) are the most commonly used imaging agents for patients with neuroendocrine tumors (NETs) in clinical practice, demonstrating good results in tumor diagnosis. For applications in peptide receptor radionuclide therapy (PRRT), targeted drugs should have high tumor uptake and prolonged tumor retention time. To enhance the uptake and retention of tracers in NETs, our goal is to design a 68Ga-labeled heterodimer for optimizing pharmacokinetics and assess whether this form is more efficacious than its monomeric equivalents. Methods: Using the somatostatin analog TATE and quinoline-based compound FAPI-46 as raw materials, we designed and synthesized 68Ga-labeled TATE-46. The labeling efficiency and stability were verified by Radio-HPLC. The receptor binding properties and tumor targeting were examined both in vitro and in vivo by using NCI-H727 (SSTR2/FAP, positive) and Mc38 (SSTR2/FAP, negative) cell lines and tumor-bearing mouse models. Preclinical evaluation was performed through cell uptake, pharmacokinetics, Micro PET, and biodistribution studies, and the results were compared with [68Ga]Ga-DOTA-TATE and [68Ga]Ga -FAPI-46. Immunohistochemistry and HE staining were performed on tumor tissues from tumor-bearing mice for further validation. Results: [68Ga]Ga-TATE-46 showed comparable SSTR2 and FAP targeting ability to monomeric TATE and FAPI-46 in cell uptake and PET imaging studies. [68Ga]Ga-TATE-46 exhibited significantly higher uptake in NCI-H727 (SSTR2/FAP, positive) tumors compared to [68Ga]Ga-DOTA-TATE (p < 0.001) and [68Ga]Ga-FAPI-46 (p < 0.001). No increased uptake of [68Ga]Ga-TATE-46 was observed in MC38 tumors (SSTR2/FAP, negative). Additionally, excess DOTA-TATE and/or unlabeled FAPI-46 significantly blocked the uptake of [68Ga]Ga-TATE-46 in NCI-H727 tumors (p < 0.001), confirming its dual-receptor targeting characteristics. The ex vivo biodistribution, immunofluorescence and immunohistochemistry results were in line with the in vivo imaging findings. Conclusion: Compared with 68Ga-labeled FAPI-46 and DOTA-TATE mono-specific tracers, the dual-target tracer [68Ga]Ga-TATE-46 improves tumor uptake, extends tumor retention, and enhances pharmacokinetics. It is an effective probe for non-invasive detection of tumors expressing FAP and SSTR2, and it is worth further studying its application in the expression of sstr2 and FAP-related tumors. Full article
(This article belongs to the Section Radiopharmaceutical Sciences)
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12 pages, 1555 KiB  
Article
Peptide Receptor Radionuclide Therapy Using 90Y- and 177Lu-DOTATATE Modulating Atherosclerotic Plaque Inflammation: Longitudinal Monitoring by 68Ga-DOTATATE Positron Emissions Tomography/Computer Tomography
by German Rubinstein, Harun Ilhan, Peter Bartenstein, Sebastian Lehner, Marcus Hacker, Andrei Todica, Mathias Johannes Zacherl and Maximilian Fischer
Diagnostics 2024, 14(22), 2486; https://doi.org/10.3390/diagnostics14222486 - 7 Nov 2024
Viewed by 1082
Abstract
Background: Atherosclerosis and its sequels, such as coronary artery disease and cerebrovascular stroke, still represent global health burdens. The pathogenesis of atherosclerosis consists of growing calcified plaques in the arterial wall and is accompanied by inflammatory processes, which are not entirely understood. This [...] Read more.
Background: Atherosclerosis and its sequels, such as coronary artery disease and cerebrovascular stroke, still represent global health burdens. The pathogenesis of atherosclerosis consists of growing calcified plaques in the arterial wall and is accompanied by inflammatory processes, which are not entirely understood. This study aims to evaluate the effect of peptide receptor radionuclide therapy (PRRT) using 90Y- and 177Lu-DOTATATE on atherosclerotic plaque inflammation. Methods: Atherosclerotic plaques in 57 cancer patients receiving PRRT using 90Y- and 177Lu-DOTATATE were longitudinally monitored by 68Ga-DOTATATE PET/CT. The target-to-background ratio (TBR) and overall vessel uptake (OVU) were measured in eight distinct arterial regions (ascending aorta, aortic arch, descending aorta, abdominal aorta, both iliac arteries, and both carotid arteries) to monitor calcified plaques. Results: PET/CT analysis shows a positive correlation between calcified plaque scores and the 68Ga-DOTATATE overall vessel uptake (OVU) in cancer patients. After PRRT, an initially high OVU was observed to decrease in the therapy group compared to the control group. An excellent correlation could be shown for each target-to-background ratio (TBR) to the OVU, especially the ascending aorta. Conclusions: The ascending aorta could present a future reference for estimating generalized atherosclerotic inflammatory processes. PRRT might represent a therapeutic approach to modulating atherosclerotic plaques. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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15 pages, 1999 KiB  
Article
Novel Detection of Pleomorphic Adenomas via Analysis of 68Ga-DOTATOC PET/CT Imaging
by Felix Johnson, Marcel Kloppenburg, Benedikt Hofauer, Barbara Wollenberg, Cosima C. Hoch, Fabian Stögbauer, Bernhard Haller, Andreas Knopf, Ulrich Strassen and Susan Notohamiprodjo
Cancers 2024, 16(15), 2624; https://doi.org/10.3390/cancers16152624 - 23 Jul 2024
Cited by 1 | Viewed by 1778
Abstract
Introduction: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. Methods: In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December [...] Read more.
Introduction: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. Methods: In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December 2021. PET/CT image assessment was compared with somatostatin receptor (SSTR) expression and histology. Results: Thirteen patients (five pleomorphic adenoma (PA) and eight other parotid lesions (OPL)) received a 68Ga-DOTATOC PET/CT. Imaging displayed strong focal tracer uptake in all PA except for one with strong tumor to background discrimination. PA revealed higher SUVmax, SUVmean, liver and blood pool quotients than those of Warthin tumors (WT) and of OPL. In comparison to the contralateral parotid, SUVmax (p = 0.02), SUVmean (p = 0.02), liver quotient (p = 0.03) and blood pool quotient (p = 0.03) were all significantly higher. In contrast, WT and OPL showed in relation to the contralateral parotid no significant differences of SUVmax (WT p = 0.79; OPL p = 0.11), SUVmean (WT p = 1.0; OPL p = 0.08), liver quotient (WT p = 0.5; OPL p = 0.08) and blood pool quotient (WT p = 0.8; OPL p = 0.19). Two PA and one granuloma were not available for examination. In the immunohistochemal analysis, all PA demonstrated the highest intensity of SSTR2 expression (grade 3). Furthermore, PA had a high percentage of cells expressing SSTR2 (20%, 80% and 55%). Conclusions: A strong tracer uptake in PA was shown in 68Ga-DOTATOC PET/CT. This may allow physicians to utilize radioligated somatostatin analogue PET CT/MR imaging to accurately diagnose PA. Additionally, it may be possible in the future to treat the PA with a noninvasive peptide receptor radionuclide therapy or with somatostatin analogues. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Salivary Gland Tumor)
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13 pages, 1175 KiB  
Article
The Clinical Utility of the NETest in Patients with Small Intestinal Neuroendocrine Neoplasms (Si-NENs): A “Real-Life” Study
by Julian Gertner, Marina Tsoli, Aimee R. Hayes, Luke Furtado O’Mahony, Faidon-Marios Laskaratos, Thomas Glover, Priyesh Karia, Mohsin F. Butt, Oliver Eastwood, Dalvinder Mandair, Martyn Caplin and Christos Toumpanakis
Cancers 2024, 16(14), 2506; https://doi.org/10.3390/cancers16142506 - 10 Jul 2024
Cited by 3 | Viewed by 1398
Abstract
Current biomarkers do not adequately predict the behaviour of neuroendocrine neoplasms (NENs). This study assessed the NETest, a multianalyte blood biomarker, in patients with small intestinal NENs (Si-NENs). We studied two patient groups: Group 1: metastatic Si-NENs (n = 102) and Group [...] Read more.
Current biomarkers do not adequately predict the behaviour of neuroendocrine neoplasms (NENs). This study assessed the NETest, a multianalyte blood biomarker, in patients with small intestinal NENs (Si-NENs). We studied two patient groups: Group 1: metastatic Si-NENs (n = 102) and Group 2: post-operatively disease-free according to 68Ga-DOTATATE PET (n = 16). NETest scores were ≤20% (normal), 21–40% (low), 41–79% (intermediate), or ≥80% (high). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In Group 1, the median NETest score was 40% (IQR: 33.3–46.7%). The NETest value (HR: 1.032, 95% CI: 1.003–1.062, p = 0.033) and high-risk NETest category (HR: 10.5, 95% CI: 1.35–81.7, p = 0.025) were independent predictors of PFS, along with presence of lung metastases, CgA levels > 10 × ULN, and tumour growth rate (TGR). Independent predictors of OS were the NETest value (HR: 1.035, 95% CI: 1.005–1.066, p = 0.024) and high-risk NETest category (HR: 15.2, 95% CI: 1.52–151, p = 0.02), along with presence of lung metastases and CgA levels > 10 × ULN. In Group 2, ROC analysis identified an AUC of 0.909 (95% CI: 0.75–0.100) for prediction of local or metastatic recurrence. Blood NETest scores were associated with PFS and OS in patients with metastatic Si-NENs, along with TGR, CgA > 10 × ULN, and presence of lung metastases. Full article
(This article belongs to the Special Issue Neuroendocrine Tumors: From Diagnosis to Therapy)
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17 pages, 376 KiB  
Review
Paragangliomas of the Head and Neck: A Review of the Latest Diagnostic and Treatment Methods
by Dragos Octavian Palade, Razvan Hainarosie, Adina Zamfir, Daniela Vrinceanu, Mihaela Pertea, Mihail Tusaliu, Florin Mocanu and Catalina Voiosu
Medicina 2024, 60(6), 914; https://doi.org/10.3390/medicina60060914 - 30 May 2024
Cited by 7 | Viewed by 4703
Abstract
Background and objectives: Paragangliomas of the head and neck are rare, slow-growing neuroendocrine tumors, benign in their vast majority, but with a possibility of developing distant metastases. They show great inheritable character, and their behavior has proven to be unpredictable; therefore, they [...] Read more.
Background and objectives: Paragangliomas of the head and neck are rare, slow-growing neuroendocrine tumors, benign in their vast majority, but with a possibility of developing distant metastases. They show great inheritable character, and their behavior has proven to be unpredictable; therefore, they are considered malignant. Material and methods: This article aims to offer a more comprehensive presentation of the pathogenesis, epidemiology, diagnostic methods, imaging development, and treatment guidelines. We tried to bring together all the necessary data that, in our opinion, a head and neck practitioner should know when managing this type of tumor. Our main focus is on the most recent studies, with the purpose of a homogenous presentation of all current guidelines and approaches to this pathology. Results: Paragangliomas of the head and neck are still a disputed topic. One of the main reasons for that is their low incidence of 0.3 to 1 per 100,000 every year. The most frequent locations are the carotid body, the temporal bone, the jugular and mastoid foramen, and the vagal nerve. Their clinical presentation usually involves a painless lateral mass associated with symptoms such as hoarseness, hearing loss, tinnitus, and cranial nerve deficits. Up to 40% of them are inherited, mostly linked with mutations of succinate dehydrogenase complex. Imaging evaluation consists of CT and MRI, and new functional explorations such as 18F-FDA and 18F-FDG PET/CT, 18F-DOPA PET, 123I-MIBG, and 68Ga-DOTATE PET/CT. Measuring the catecholamine levels in the plasma and urine is mandatory, even though paragangliomas of the head and neck rarely display secretory behavior. Treatment mainly consists of surgery, with different approaches and techniques, but conservative management methods such as wait and scan, radiotherapy, proton therapy, and chemotherapy have proven their efficiency. The therapeutical decision lacks consensus, and current studies tend to recommend an individualized approach. Guidelines regarding long-term follow-up are still a matter of debate. Full article
18 pages, 1127 KiB  
Review
Prostate-Specific Membrane Antigen Positron Emission Tomography Oncological Applications beyond Prostate Cancer in Comparison to Other Radiopharmaceuticals
by Alberto Miceli, Virginia Liberini, Giovanna Pepe, Francesco Dondi, Antonio Vento, Lorenzo Jonghi Lavarini, Greta Celesti, Maria Gazzilli, Francesca Serani, Priscilla Guglielmo, Ambra Buschiazzo, Rossella Filice, Pierpaolo Alongi, Riccardo Laudicella and Giulia Santo
Diagnostics 2024, 14(10), 1002; https://doi.org/10.3390/diagnostics14101002 - 13 May 2024
Cited by 5 | Viewed by 2609
Abstract
Background: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed on the surface of tumor cells in most of the patients affected by prostate adenocarcinoma (PCa). However, PSMA expression has also been demonstrated in the endothelial cells of newly formed vessels [...] Read more.
Background: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed on the surface of tumor cells in most of the patients affected by prostate adenocarcinoma (PCa). However, PSMA expression has also been demonstrated in the endothelial cells of newly formed vessels of various solid tumors, suggesting a role for PSMA in neoangiogenesis. In this scenario, gallium-68 (68Ga) or fluoro-18 (18F)-labeled PSMA positron emission tomography (PET) may play a role in tumors other than PCa, generally evaluated employing other radiopharmaceuticals targeting different pathways. This review aims to investigate the detection rate of PSMA-PET compared to other radiopharmaceuticals (especially [18F]FDG) in non-prostate tumors to identify patients who may benefit from the use of such a theragnostic agent. Methods: We performed a bibliographic search on three different databases until February 2024 using the following terms: “positron emission tomography”, “PET”, “PET/CT”, “Prostate-specific membrane antigen”, “PSMA”, “non-prostate”, “not prostate cancer”, “solid tumor”, “FDG”, “Fluorodeoxyglucose”, “FAPi”, “FET”, “MET”, “DOPA”, “choline”, “FCH”, “FES”, “DOTATOC”, “DOTANOC”, and “DOTATATE”. Only original articles edited in English with at least 10 patients were included. Results: Out of a total of 120 articles, only 25 original articles comparing PSMA with other radiotracers were included in this study. The main evidence was demonstrated in renal cell carcinoma, where PSMA showed a higher detection rate compared to [18F]FDG PET/CT, with implications for patient management. PSMA PET may also improve the assessment of other entities, such as gliomas, in defining regions of early neoangiogenesis. Further data are needed to evaluate the potential role of PSMA-PET in triple-negative breast cancer as a novel therapeutic vascular target. Finally, unclear applications of PSMA-PET include thyroid and gastrointestinal tumors. Conclusions: The present review shows the potential use of PSMA-labeled PET/CT in solid tumors beyond PCa, underlining its value over other radiopharmaceuticals (mainly [18F]FDG). Prospective clinical trials with larger sample sizes are crucial to further investigate these possible clinical applications. Full article
(This article belongs to the Special Issue The Use of PSMA in Nuclear Medicine beyond Prostate Cancer)
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