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Keywords = Lu-177-DOTA-TATE

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19 pages, 6583 KiB  
Case Report
New Horizons: The Evolution of Nuclear Medicine in the Diagnosis and Treatment of Pancreatic Neuroendocrine Tumors—A Case Report
by Annamária Bakos, László Libor, Béla Vasas, Kristóf Apró, Gábor Sipka, László Pávics, Zsuzsanna Valkusz, Anikó Maráz and Zsuzsanna Besenyi
J. Clin. Med. 2025, 14(13), 4432; https://doi.org/10.3390/jcm14134432 - 22 Jun 2025
Viewed by 523
Abstract
Background: Pancreatic neuroendocrine tumors (PanNETs) are relatively rare neoplasms with heterogeneous behavior, ranging from indolent to aggressive disease. The evolution of nuclear medicine has allowed the development of an efficient and advanced toolkit for the diagnosis and treatment of PanNETs. Case: [...] Read more.
Background: Pancreatic neuroendocrine tumors (PanNETs) are relatively rare neoplasms with heterogeneous behavior, ranging from indolent to aggressive disease. The evolution of nuclear medicine has allowed the development of an efficient and advanced toolkit for the diagnosis and treatment of PanNETs. Case: A 45-year-old woman was diagnosed with a grade 1 PanNET and multiple liver metastases. She underwent distal pancreatectomy with splenectomy, extended liver resection, and radiofrequency ablation (RFA). Surgical planning was guided by [99mTc]Tc-EDDA/HYNIC-TOC SPECT/CT (single-photon emission computed tomography/computed tomography) and preoperative [99mTc]Tc-mebrofenin-based functional liver volumetry. Functional liver volumetry based on dynamic [99mTc]Tc-mebrofenin SPECT/CT facilitated precise surgical planning and reliable assessment of the efficacy of parenchymal modulation, thereby aiding in the prevention of post-hepatectomy liver failure. Liver fibrosis was non-invasively evaluated using two-dimensional shear wave elastography (2D-SWE). Tumor progression was monitored using somatostatin receptor scintigraphy, chromogranin A, and contrast-enhanced CT. Recurrent disease was treated with somatostatin analogues (SSAs) and [177Lu]Lu-DOTA-TATE peptide receptor radionuclide therapy (PRRT). Despite progression to grade 3 disease (Ki-67 from 1% to 30%), the patient remains alive 53 months post-diagnosis, in complete remission, with an ECOG (Eastern Cooperative Oncology Group) status of 0. Conclusions: Functional imaging played a pivotal role in guiding therapeutic decisions throughout the disease course. This case not only underscores the clinical utility of advanced nuclear imaging but also illustrates the dynamic nature of pancreatic neuroendocrine tumors. The transition from low-grade to high-grade disease highlights the need for further studies on tumor progression mechanisms and the potential role of adjuvant therapies in managing PanNETs. Full article
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13 pages, 1106 KiB  
Systematic Review
Peptide Receptor Radionuclide Therapy in Patients with Advanced, Recurrent or Progressive Meningioma: An Updated Systematic Review and Meta-Analysis
by Barbara Muoio, Cesare Michele Iacovitti, Davide Giovanni Bosetti, Maddalena Sansovini, Marco Cuzzocrea, Gaetano Paone and Giorgio Treglia
Cancers 2025, 17(12), 2039; https://doi.org/10.3390/cancers17122039 - 18 Jun 2025
Viewed by 714
Abstract
Background: Peptide receptor radionuclide therapy (PRRT) could be a therapeutic option for patients with advanced, recurrent or progressing meningiomas overexpressing somatostatin receptors. The aim of this study is to perform an updated meta-analysis to establish the disease control rate of PRRT in these [...] Read more.
Background: Peptide receptor radionuclide therapy (PRRT) could be a therapeutic option for patients with advanced, recurrent or progressing meningiomas overexpressing somatostatin receptors. The aim of this study is to perform an updated meta-analysis to establish the disease control rate of PRRT in these patients. Methods: A comprehensive literature search of studies on PRRT in patients with advanced, recurrent or progressing meningioma was carried out. Four different databases (PubMed/MEDLINE, EMBASE, Cochrane library, Google Scholar) were screened until April 2025. Only original articles about PRRT in advanced, progressive or refractory meningiomas were selected. Case reports were excluded. Three review authors independently performed the literature search, the article selection and the data extraction. Main findings of eligible studies were summarized and a proportion meta-analysis on the disease control rate was carried out using a random-effects model. Results: In total, 18 studies (269 patients) published from 2006 to 2025 were included in the analysis. In most of the included studies, PRRT was performed using [177Lu]Lu-DOTATATE. The pooled disease control rate was 67.7% (95% confidence interval values: 59.6–75.7%). PRRT was well-tolerated in most patients with advanced, recurrent or progressive meningioma. Moderate statistical heterogeneity was found in the meta-analysis (I-square: 53%). Conclusions: PRRT is an effective and well-tolerated treatment in patients with advanced, progressive or recurrent meningiomas, showing a significant disease control rate (in about two-thirds of patients). Even if well-designed clinical trials are needed to corroborate these findings, evidence-based data seem to support the clinical use of PRRT for this indication. Full article
(This article belongs to the Special Issue Novel Targeted Therapies in Brain Tumors)
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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 773
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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15 pages, 2725 KiB  
Article
Comparison of the Hematotoxicity of PRRT with Lutathera® and Locally Manufactured 177Lu-HA-DOTATATE in Patients with Neuroendocrine Tumors and the Impact of Different Application Intervals
by Markus Hofmann, Sophie C. Kunte, Marcus Unterrainer, Astrid Delker, Adrien Holzgreve, Johannes Toms, Franz Joseph Gildehaus, Christoph J. Auernhammer, Christine Spitzweg, Mathias J. Zacherl, Harun Ilhan, Johannes Rübenthaler, Leonie Beyer and Lena M. Unterrainer
Cancers 2025, 17(9), 1423; https://doi.org/10.3390/cancers17091423 - 24 Apr 2025
Cited by 2 | Viewed by 860
Abstract
Background/Objectives: Peptide Receptor Radionuclide Therapy (PRRT) is approved for patients with inoperable, progressive and/or metastatic well-differentiated NETs. Before the approval of Lutathera®, locally manufactured 177Lu-HA-DOTATATE was used on a regular basis in clinical routine. The aim of this study was [...] Read more.
Background/Objectives: Peptide Receptor Radionuclide Therapy (PRRT) is approved for patients with inoperable, progressive and/or metastatic well-differentiated NETs. Before the approval of Lutathera®, locally manufactured 177Lu-HA-DOTATATE was used on a regular basis in clinical routine. The aim of this study was (1) to compare the hematotoxicity of locally manufactured 177Lu-HA-DOTATATE with Lutathera® in GEP-NET patients and (2) to compare the recommended treatment interval of 8 weeks between each cycle to a prolonged scheme of up to 11 weeks for both 177Lu-HA-DOTATATE and Lutathera®. Methods: The included patients with GEP NETs (n = 46) received four cycles of PRRT, either 177Lu-HA-DOTATATE or Lutathera®, and were divided into four subgroups. The subgroups were treated with either locally manufactured 177Lu-HA-DOTATATE or Lutathera® and were stratified into a mean application interval of 8 (HA8weeks, n = 10/Lutathera8weeks, n = 16) or 11 weeks (HAadapted, n = 10/Lutatheraadapted, n = 10). To evaluate therapy associated hemato- and nephrotoxicity, patients underwent two laboratory follow-up examinations (follow-up 1—between 2./3. therapy cycle; follow-up 2—after the termination of the 4. therapy cycle) and were then compared to pre-PRRT laboratory results. To assess hematological and renal recovery trends, blood values and parameters of kidney function were collected up to 58.9 weeks after PRRT completion. Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) were used for grading hematological parameters. Results: The occurrence of high-grade adverse events (CTCAE grade 3/4) after PRRT was moderate, with 1/10 (10%) grade 4 lymphocytopenia in the Lutatheraadapted group, while overall, 20/46 (43.5%) patients had grade 3 lymphocytopenia. Grade 3 thrombocytopenia occurred in 1/10 (10%) patients of the HAadapted group. Absolute and percentage changes in the kidney function (creatinine, TER) remained constant during PRRT in all subgroups. All four subgroups showed a significant decrease in absolute blood value changes for PLT counts, WBC counts, neutrophil granulocytes and lymphocytes between, prior to and after PRRT (p < 0.05, each). Regarding percentage changes in laboratory parameters, only the HAadapted and the HA8weeks groups had significant decreases in WBC (p < 0.03, each) and PLT counts (p < 0.04, each) while there was no significant degradation of any other hematological parameter in any of the subgroups. Only patients with longer treatment intervals under 177Lu-HA-DOTATATE therapy showed a statistically significant correlation in the long-term recovery analysis concerning the PLT counts (r = 0.6, p < 0.0001). Other blood and kidney values showed no significant correlation in the long-term analysis in the other subgroups. Conclusion: Comparing the hematotoxicity in patients that were treated with locally manufactured 177Lu-HA-DOTATATE with patients that were treated with Lutathera® and assessing different treatment intervals in both groups (8 vs. 11 weeks), revealed that there is overall a low to moderate incidence of significant changes in hematological and renal parameters directly after PRRT. Recovery trends of hematological and renal parameters after 1 year suggest that patients treated with locally manufactured 177Lu-HA-DOTATATE might benefit from a longer treatment interval of 11 weeks regarding their PLT counts. Given the risk of developing hematological diseases such as therapy-related myeloid neoplasms years after PRRT, longer observational periods after PRRT will be crucial. Full article
(This article belongs to the Special Issue Oncology: State-of-the-Art Research in Germany)
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15 pages, 2238 KiB  
Article
Evaluation of the Real-Life Efficacy and Safety of the Treatment with Lutetium-177 Dotatate for Metastatic Neuroendocrine Tumors
by Sara Elena Campos Ramírez, Alejandro Andrés García, Carmen Blanco Abad, Paula Gomila Pons, Pablo Gómez Mugarza, Sofía Elena Ruffini Egea, Luis Gallart Caballero, Eduardo Polo Marques and Vicente Alonso Orduña
J. Clin. Med. 2025, 14(7), 2384; https://doi.org/10.3390/jcm14072384 - 30 Mar 2025
Viewed by 1932
Abstract
Background: Therapy using lutetium-177 dotatate (177LU) was approved in Europe for the treatment of advanced neuroendocrine tumors (NETs) in 2017. Since then, it has become part of the strategies in the treatment of NETs, making it now possible to evaluate real-life [...] Read more.
Background: Therapy using lutetium-177 dotatate (177LU) was approved in Europe for the treatment of advanced neuroendocrine tumors (NETs) in 2017. Since then, it has become part of the strategies in the treatment of NETs, making it now possible to evaluate real-life results. Research Design and Methods: Single-arm, retrospective, multicenter, cohort study of all the patients with metastatic NETs treated with 177LU (four cycles of 200 mCi every 8 weeks) in the two medical centers dedicated to the treatment of NETs from the region of Aragón, Spain, from 2017 to 2024. Descriptive analysis of demographic characteristics, efficacy, and survival analysis were performed using the statistics software Jamovi 2.6.14. Results: Sixty-eight patients were included. The majority were male, and the most frequent primary location was the pancreas. The ORR was 30.9%. The DCR was 88%. The median OS was 47.4 months [95% CI, 25.6–NE]. The median PFS was 26.1 months [95% CI, 18.5–68.3]. High-grade tumors, multiple previous treatments, and pancreatic location presented worse OS. In total, 42.6% presented any grade adverse event (17.2% hematologic, 30.9% GI symptoms). Conclusions: The efficacy of 177LU in our study is like that observed in similar studies. Acceptable tolerance has been shown. Pancreatic tumors, previous treatments, and higher grades demonstrated worse outcomes. The new research line must consider the use of treatment with 177LU in earlier lines for metastatic disease as well as its possible use in local or locally advanced disease. Full article
(This article belongs to the Section Oncology)
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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 2457
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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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 1344
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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13 pages, 1217 KiB  
Article
Hematological Side Effects of 177Lu-DOTA-TATE Therapy in Patients with NENs
by Luciano Carideo, Rosaria Meucci, Giuseppe Campagna, Vincenzo Marcello Russo, Enrico D’Ippolito, Maria Rinzivillo, Francesco Panzuto and Daniela Prosperi
Hemato 2025, 6(1), 1; https://doi.org/10.3390/hemato6010001 - 30 Dec 2024
Viewed by 2202
Abstract
Background/Objectives: Lutathera® ([177Lu]Lu-DOTA-TATE) is the first radiolabelled somatostatin (SST) analog approved for the treatment of patients with well-differentiated (G1 and G2) unresectable or metastatic gastro-entero-pancreatic neuro-endocrine-neoplasms (GEP-NENs). The bone marrow and kidneys are critical organs for RLT with [ [...] Read more.
Background/Objectives: Lutathera® ([177Lu]Lu-DOTA-TATE) is the first radiolabelled somatostatin (SST) analog approved for the treatment of patients with well-differentiated (G1 and G2) unresectable or metastatic gastro-entero-pancreatic neuro-endocrine-neoplasms (GEP-NENs). The bone marrow and kidneys are critical organs for RLT with [177Lu]Lu-DOTA-TATE. Our purpose was to evaluate hematological and renal toxicity in 29 patients (18 males, 11 females) treated with Lutathera®. Methods: According to standard protocols, four cycles of (177Lu)Lu-DOTA-TATE were administered every eight/nine weeks. Patients received pre-medication with anti-emetic and anti-acid drugs and a slow amino acid infusion for renal protection. Blood count and serum creatinine data were collected at three time points: before the first cycle, after the second cycle, and at the end of treatment. Results: We found that almost all hematological parameters significantly decreased between the baseline and/or interim and post-therapy evaluation, although without a clinical impact. The presence of total tumor load or bone metastases had no influence on these findings, while male patients showed less hematological toxicity than females. Conversely, creatinine levels did not vary during treatment. Conclusions: Our study confirms that [177Lu]Lu-DOTATATE RLT is safe and well tolerated despite some minor (grade 1) hematological toxicity. Full article
(This article belongs to the Section Radiolabeled Blood Elements and Other Imaging Modalities)
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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 1096
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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13 pages, 679 KiB  
Article
Adverse Events of Radioligand Therapy in Patients with Progressive Neuroendocrine Neoplasms: The Biggest Eastern European Prospective Study
by Adam Daniel Durma, Marek Saracyn, Maciej Kołodziej, Katarzyna Jóźwik-Plebanek, Dorota Brodowska-Kania, Beata Dmochowska, Adrianna Mróz, Beata Kos-Kudła and Grzegorz Kamiński
Cancers 2024, 16(20), 3509; https://doi.org/10.3390/cancers16203509 - 17 Oct 2024
Cited by 1 | Viewed by 1163
Abstract
Background: Neuroendocrine neoplasms (NENs) are neoplastic tumors developing in every part of the body, mainly in the gastrointestinal tract and pancreas. Their treatment involves the surgical removal of the tumor and its metastasis, long-acting somatostatin analogs, chemotherapy, targeted therapy, and radioligand therapy (RLT). [...] Read more.
Background: Neuroendocrine neoplasms (NENs) are neoplastic tumors developing in every part of the body, mainly in the gastrointestinal tract and pancreas. Their treatment involves the surgical removal of the tumor and its metastasis, long-acting somatostatin analogs, chemotherapy, targeted therapy, and radioligand therapy (RLT). Materials and Methods: A total of 127 patients with progressive neuroendocrine neoplasms underwent RLT—4 courses, administered every 10 weeks—with the use of 7.4 GBq [177Lu]Lu-DOTA-TATE or tandem therapy with 1.85 GBq [177Lu]Lu-DOTA-TATE and 1.85 GBq [90Y]Y-DOTA-TATE. Assessment of short- and long-term complications, as well as the calculation of progression-free survival (PFS) and overall survival (OS) were performed. Results: RLT caused a statistically but not clinically significant decrease in blood morphology parameters during both short- and long-term observations. Glomerular filtration rate (GFR) significantly decreased only in a long-term observation after RLT; however, it was clinically acceptable. Computed predictions of progression-free survival (PFS) and overall survival (OS) indicated that five years post-RLT, there is a 74% chance of patients surviving, with only a 58.5% likelihood of disease progression. Conclusions: Computed predictions of PFS and OS confirmed treatment efficiency and good patient survival. RLT should be considered a safe and reliable line of treatment for patients with progressive NENs as it causes only a low number of low-grade adverse events. Full article
(This article belongs to the Special Issue Radioligand Therapy (RLT) in Neuroendocrine Neoplasms)
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13 pages, 2268 KiB  
Article
The Safety and Efficacy of Peptide Receptor Radionuclide Therapy for Gastro-Entero-Pancreatic Neuroendocrine Tumors: A Single Center Experience
by Leandra Piscopo, Emilia Zampella, Fabio Volpe, Valeria Gaudieri, Carmela Nappi, Erica Di Donna, Stefania Clemente, Antonio Varallo, Mariano Scaglione, Alberto Cuocolo and Michele Klain
Curr. Oncol. 2024, 31(9), 5617-5629; https://doi.org/10.3390/curroncol31090416 - 18 Sep 2024
Viewed by 1499
Abstract
The aim of the present study was to evaluate the safety and efficacy of radionuclide therapy with [177Lu]Lu-DOTA-TATE according to our single center experience at the University of Naples Federico II. For the present analysis, we considered 21 patients with progressive, [...] Read more.
The aim of the present study was to evaluate the safety and efficacy of radionuclide therapy with [177Lu]Lu-DOTA-TATE according to our single center experience at the University of Naples Federico II. For the present analysis, we considered 21 patients with progressive, advanced, well-differentiated G1 and G2 in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) treated with [177Lu]Lu-DOTA-TATE according to the decisions of a multidisciplinary team. All patients underwent four cycles of 7–8 GBq of [177Lu]Lu-DOTA-TATE every 8 weeks. A whole-body scan (WBS) was performed 4, 48, and 168 h after each treatment. The dosimetry towards the organ at risk and target lesions was calculated. For each patient, renal and bone marrow parameters were evaluated before, during, and 3 months after the end of the treatment. Follow-up data were obtained and RECIST criteria were considered as the endpoint. Among 21 patients enrolled (mean age 65 ± 9 years); 17 (81%) were men and the small intestine was the most frequent location of disease (n = 12). A mild albeit significant variation (p < 0.05) in both platelets and white blood cell counts among all time points was observed, despite it disappearing 3 months after the end of the therapy. According to the RECIST criteria, 11 (55%) patients had a partial response to therapy and 8 (40%) had stable disease. Only one (5%) patient had disease progression 4 months after treatment. Our data confirm that [177Lu]Lu-DOTA is safe and effective in controlling the burden disease of G1/G2 GEP-NETs patients. Full article
(This article belongs to the Special Issue Application of Nuclear Medicine in Cancer Diagnosis and Treatment)
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8 pages, 1496 KiB  
Article
Safety and Efficacy of Peptide Receptor Radionuclide Therapy (PRRT) Following Bland Embolization for Metastatic Neuroendocrine Tumors
by Adam Alayli, Hoang Ngo, Dhiraj Sikaria, Altan Ahmed, Elias Salloum, Jonathan R. Strosberg, Taymeyah E. Al-Toubah, Bela Kis, Mintallah Haider and Ghassan El-Haddad
Cancers 2024, 16(15), 2703; https://doi.org/10.3390/cancers16152703 - 30 Jul 2024
Cited by 1 | Viewed by 1611
Abstract
Rationale: Evaluating the long-term safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumors (mNETs) who have undergone prior bland hepatic transarterial embolization (TAE). Methods: Retrospective review of mNET patients who received PRRT with 177Lu-DOTATATE [...] Read more.
Rationale: Evaluating the long-term safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumors (mNETs) who have undergone prior bland hepatic transarterial embolization (TAE). Methods: Retrospective review of mNET patients who received PRRT with 177Lu-DOTATATE between 4/2018 and 02/2022 with and without prior TAE. The most recent clinical, imaging, and laboratory findings, including hepatic Common Terminology Criteria for Adverse Events v5.0, were compared to pre-PRRT. Results: 171 patients (95 M, 76 F, median age = 66) with mNET of different primary sites (9 foregut, 100 midgut, 9 hindgut, 44 pancreas, 9 unknown) received at least 1 cycle of PRRT with at least 6 months of follow-up, 110 of whom were embolization-naïve and 61 who had prior TAE. The median follow up was 22 months (range: 6–43). Patients with prior TAE had higher liver tumor burden on average than patients without prior TAE; however, the difference was not statistically significant (p = 0.06). There was no significant difference in the rates of G3 or G4 hepatotoxicity (p = 0.548 and p = 0.999, respectively) in patients who underwent prior TAE and those who were TAE-naïve. The hepatic progression-free survival was 22.9 months in TAE-naïve patients and 25.7, 20.2, and 12.8 months in patients with 1, 2, and 3 prior TAE treatments, respectively. Conclusion: Peptide receptor radionuclide therapy following transarterial bland embolization for mNET is safe and effective. Full article
(This article belongs to the Special Issue Updates in Neuroendocrine Neoplasms)
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16 pages, 4878 KiB  
Article
Investigating the Radiobiological Response to Peptide Receptor Radionuclide Therapy Using Patient-Derived Meningioma Spheroids
by Thom G. A. Reuvers, Vivian Grandia, Renata M. C. Brandt, Majd Arab, Sybren L. N. Maas, Eelke M. Bos and Julie Nonnekens
Cancers 2024, 16(14), 2515; https://doi.org/10.3390/cancers16142515 - 11 Jul 2024
Cited by 2 | Viewed by 1769
Abstract
Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients. However, current knowledge of the underlying radiation biology is limited, in part due to the lack of appropriate in vitro models. Here, we demonstrate proof-of-concept [...] Read more.
Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients. However, current knowledge of the underlying radiation biology is limited, in part due to the lack of appropriate in vitro models. Here, we demonstrate proof-of-concept of a meningioma patient-derived 3D culture model to assess the short-term response to radiation therapies such as PRRT and external beam radiotherapy (EBRT). We established short-term cultures (1 week) for 16 meningiomas with high efficiency and yield. In general, meningioma spheroids retained characteristics of the parental tumor during the initial days of culturing. For a subset of tumors, clear changes towards a more aggressive phenotype were visible over time, indicating that the culture method induced dedifferentiation of meningioma cells. To assess PRRT efficacy, we demonstrated specific uptake of 177Lu-DOTA-TATE via somatostatin receptor subtype 2 (SSTR2), which was highly overexpressed in the majority of tumor samples. PRRT induced DNA damage which was detectable for an extended timeframe as compared to EBRT. Interestingly, levels of DNA damage in spheroids after PRRT correlated with SSTR2-expression levels of parental tumors. Our patient-derived meningioma culture model can be used to assess the short-term response to PRRT and EBRT in radiobiological studies. Further improvement of this model should pave the way towards the development of a relevant culture model for assessment of the long-term response to radiation and, potentially, individual patient responses to PRRT and EBRT. Full article
(This article belongs to the Section Cancer Therapy)
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7 pages, 7206 KiB  
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Impressive Response to TANDEM Peptide Receptor Radionuclide Therapy with 177Lu/225AcDOTA-LM3 Somatostatin Receptor Antagonist in a Patient with Therapy-Refractory, Rapidly Progressive Neuroendocrine Neoplasm of the Pancreas
by Elisabetta Perrone, Kriti Ghai, Aleksandr Eismant, Mikkel Andreassen, Seppo W. Langer, Ulrich Knigge, Andreas Kjaer and Richard P. Baum
Diagnostics 2024, 14(9), 907; https://doi.org/10.3390/diagnostics14090907 - 26 Apr 2024
Cited by 7 | Viewed by 2582
Abstract
The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [...] Read more.
The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE, Lanreotide, Everolimus, and liver embolization. Due to severe disease progression, after a liver biopsy revealing tumor grade G3, PRRT with the somatostatin receptor antagonist LM3 was initiated. [68Ga]GaDOTA-LM3 PET/CT showed intense tracer uptake in the liver, pancreatic tumor, lymph nodes, and bone metastases. Three TANDEM-PRRT cycles using [177Lu]LuDOTA-LM3 and [225Ac]AcDOTA-LM3, administered concurrently, resulted in significant improvement, notably in liver metastases, hepatomegaly reduction, the complete regression of bone and lymph node metastases, and primary tumor improvement. Partial remission was confirmed by positron emission tomography/computed tomography, chest–abdomen–pelvis contrast-enhanced computed tomography, and magnetic resonance of the abdomen, with marked clinical improvement in pain, energy levels, and quality of life, enabling full resumption of physical activity. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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11 pages, 2769 KiB  
Article
Effects of Peptide Receptor Radiotherapy in Patients with Advanced Paraganglioma and Pheochromocytoma: A Nation-Wide Cohort Study
by Linda Skibsted Kornerup, Mikkel Andreassen, Ulrich Knigge, Anne Kirstine Arveschoug, Per Løgstup Poulsen, Andreas Kjær, Peter Sandor Oturai, Henning Grønbæk and Gitte Dam
Cancers 2024, 16(7), 1349; https://doi.org/10.3390/cancers16071349 - 29 Mar 2024
Cited by 2 | Viewed by 1890
Abstract
Introduction: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia. Management of disseminated or metastatic pheochromocytomas and paragangliomas continues to pose challenges and relies on limited evidence. Method: In this study, we [...] Read more.
Introduction: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia. Management of disseminated or metastatic pheochromocytomas and paragangliomas continues to pose challenges and relies on limited evidence. Method: In this study, we report retrospective data on median overall survival (OS) and median progression-free survival (PFS) for all Danish patients treated with peptide receptor radionuclide therapy (PRRT) with 177Lu-Dotatate or 90Y-Dotatate over the past 15 years. One standard treatment of PRRT consisted of 4 consecutive cycles with 8–14-week intervals. Results: We included 28 patients; 10 were diagnosed with pheochromocytoma and 18 with paraganglioma. Median age at first PRRT was 47 (IQR 15–76) years. The median follow-up time was 31 (IQR 17–37) months. Eight patients died during follow-up. Median OS was 72 months, and 5-year survival was 65% with no difference between pheochromocytoma and paraganglioma. Patients with germline mutations had better survival than patients without mutations (p = 0.041). Median PFS after the first cycle of PRRT was 30 months. For patients who previously received systemic treatment, the median PFS was 19 months, compared with 32 months for patients with no previous systemic treatment (p = 0.083). Conclusions: The median OS of around 6 years and median PFS of around 2.5 years found in this study are comparable to those reported in previous studies employing PRRT. Based on historical data, the efficacy of PRRT may be superior to 131I-MIBG therapy, and targeted therapy with sunitinib and PRRT might therefore be considered as first-line treatment in this patient group. Full article
(This article belongs to the Special Issue Neuroendocrine Tumors: From Diagnosis to Therapy)
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