Peptide receptor radionuclide therapy for GEP-NET: consolidated knowledge and innovative applications

Telo, Silvi; Filice, Angelina; Versari, Annibale; Campana, Davide; Calabrò, Diletta; Fanti, Stefano; Ambrosini, Valentina

doi:10.1007/s40336-021-00443-y

Cited by 3 publications

(4 citation statements)

References 91 publications

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“…In order to improve PRRT efficacy, the administration of the tracer directly into the hepatic artery [ 21 ] was suggested. In particular, patients with hepatic dominant metastases would benefit from this approach due to an increase of uptake of the radiopharmaceutical [ 22 ].…”

Section: Ga-dota-conjugated Peptidesmentioning

confidence: 99%

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms

Fortunati

Argalia

Zanoni

et al. 2022

Curr. Treat. Options in Oncol.

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Opinion statementNeuroendocrine neoplasms (NEN) are a heterogeneous group of tumours derived from cells of neuroendocrine origin and can potentially arise everywhere in the human body. The diagnostic assessment of NEN can be performed using a variety of PET radiopharmaceuticals. Well-differentiated NEN (NET) present a high expression of SSTR (somatostatin receptors) and can therefore be studied with 68Ga-DOTA-peptides ([68Ga]Ga-DOTANOC, [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTATATE). Current guidelines recommend the use of SSTR imaging to assess disease extension at staging/restaging, follow-up, assessment of response to therapy and selection of patients who may benefit from radionuclide therapy (PRRT). [18F]F-FDG is used for the assessment of high-grade tumours (high-grade G2, G3 and NEC) and in every case, there is one or more mismatched lesions between diagnostic CT (positive) and SSTR-PET/CT (negative). [18F]F-DOPA is currently used for the assessment of medullary thyroid carcinoma, neuroblastoma, primary pheochromocytoma and abdominal paraganglioma. In recent years, however, several new tracers were designed exploiting the many potential targets of the neuroendocrine cell and were employed in clinical trials for both imaging and therapy. Currently, the real-life clinical impact of these tracers is still mostly not known; however, the favourable biodistribution (e.g. [68Ga]Ga-FAPI, SSTR antagonists) and the possibility to use new theranostic pairs may provide novel diagnostic as well as therapeutic options (e.g. [68Ga]Ga-PSMA, [64Cu]Cu-SARTATE, [68Ga]Ga-CXCR4) for NEN patients.

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Section: Ga-dota-conjugated Peptidesmentioning

confidence: 99%

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms

Fortunati

Argalia

Zanoni

et al. 2022

Curr. Treat. Options in Oncol.

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“…To increase the damage caused by radiation to tumor cells and increase their killing, different radiosensitizers can be administered concomitantly to PRRT. One way to achieve this aim—and the most extensively explored way—is to combine PRRT with chemotherapy, such as a fluoropyrimidine, namely, 5-fluorourcil (5FU) or capecitabine (CAP) and/or temozolomide (TEM) [ 164 , 172 ]. Peptide receptor chemo-radionuclide therapy (PRCRT) in patients with well-differentiated GEP NETs treated within early-phase clinical trials provided ORRs as high as 24–53% [ 173 , 174 , 175 ], which also exceeded 80% in the subgroup of patients with pancreatic NETs receiving PRCRT with TEM—likely because of the role of MGMT (O(6)-methylguanine-DNA methyltransferase) promoter methylation in these patients [ 176 ].…”

Section: Somatostatin Analogues For Targeted Therapymentioning

confidence: 99%

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

Ambrosini

Zanoni

Filice

et al. 2022

Cancers

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Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with [68Ga] for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.

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“…A high SSTR density thus correlates with an improved response to PRRT and better prognosis (20). Because of weak or absent SSTR expression, as well as being generally more aggressive, higher-grade NETs and poorly differentiated neuroendocrine cancers have a worse prognosis (22). SSTR positivity for all lesions should be confirmed with SSTR imaging before 177 Lu-DOTATATE therapy; PETbased SSTR imaging (DOTATATE, DOTATOC, DOTA-NOC) has become the standard of care and is preferred over 111 In-pentetreotide scintigraphy because of the higher spatial resolution and dramatically improved lesion detectability of these agents (23).…”

Section: Patient Selectionmentioning

confidence: 99%

“…In this patient population, multidisciplinary teams may consider the addition of concomitant chemotherapy to a PRRT regimen. Higher-grade NETs (grades 2 or 3) are currently being evaluated in the phase III NETTER-2 trial, which is investigating PRRT as first-line therapy when used in combination with long-acting, high-dose octreotide (22). The phase III COMPETE trial is currently comparing 4 cycles of 7.4 GBq (200 mCi) of 177 Lu-DOTATOC with daily everolimus administration in patients with SSTR-positive disease (25).…”

Section: Patient Selectionmentioning

confidence: 99%

Practical Considerations for Implementation of ¹⁷⁷Lu-DOTATATE Neuroendocrine Tumor Treatment Programs

Soulek

Mastascusa

Martin

et al. 2022

J. Nucl. Med. Technol.

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CE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org. Complete the test online no later than September 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.The 2018 Food and Drug Administration approval of 177 Lu-DOTA-TATE for the treatment of somatostatin receptor-positive neuroendocrine tumors (NETs) represents a paradigm-shifting approach to cancer treatments around the globe. Gastroenteropancreatic NETs overexpress the somatostatin subtype receptor 2, which is now exploited for receptor-based imaging and therapy, thus generating significant progress in the diagnosis and treatment of this orphan disease. The recent Food and Drug Administration approval of receptor-based PET radiopharmaceuticals and a new peptide receptor radiopharmaceutical therapy, 177 Lu-DOTATATE, has dramatically impacted NET patient management. The focus of this paper is to review clinical considerations associated with implementing a 177 Lu-DOTATATE program. We review receptor-based NET radiopharmaceuticals; 177 Lu-DOTATATE patient selection criteria; administration methods; clinical, regulatory, and radiation safety considerations; technical factors; tissue dosimetry; and reimbursement guidelines.

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Peptide receptor radionuclide therapy for GEP-NET: consolidated knowledge and innovative applications

Cited by 3 publications

References 91 publications

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

Practical Considerations for Implementation of ¹⁷⁷Lu-DOTATATE Neuroendocrine Tumor Treatment Programs

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Peptide receptor radionuclide therapy for GEP-NET: consolidated knowledge and innovative applications

Cited by 3 publications

References 91 publications

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

Practical Considerations for Implementation of 177Lu-DOTATATE Neuroendocrine Tumor Treatment Programs

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Practical Considerations for Implementation of ¹⁷⁷Lu-DOTATATE Neuroendocrine Tumor Treatment Programs