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

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Abstract

Purpose

Aim of the present review is to analyze the most relevant achievements of peptide receptor radionuclide therapy (PRRT) in neuroendocrine neoplasms (NENs) management, focusing on treatment efficacy as well as toxicity and taking into account the innovative applications and future perspectives.

Methods

A comprehensive literature review of PubMed/Medline (last updated January 2021) was performed using a combination of the following keywords: PRRT, NEN/NET treatment, somatostatin analogues, PET/CT [68Ga]Ga-DOTA-peptides (DOTATATE, DOTATOC, DOTANOC), [18F]FDG. Case reports, editorials, letters to the editor and articles not specifically addressing PRRT achievements were excluded. Only papers in English were considered.

Results

Published data showed that PRRT has been increasingly used for treatment of well-differentiated neuroendocrine tumours (NETs). Preliminary results from early studies were difficult to compare due to different treatment regimens in often small and heterogeneous patients’ populations. Recently, the regulatory agencies approved [177Lu]Lu-DOTA-TATE for treatment of well-differentiated gastro-entero-pancreatic neuroendocrine tumours G1-G2 (GEP-NET). Patients treated with PRRT show good response rates (range 66–95% considering total objective response and stable disease). Regarding toxicity, a significant reduction of renal absorbed dose (ranging from 9 to 53%) has been reported using kidney protection strategies. Moreover, the incidence of haematological long-term toxicity has been reported in many studies but toxicity is mild and transient in most patients while severe toxicity, such as acute leukemia (AL) and myelodysplastic syndrome (MDS), were reported in less than 3% of patients. However, several issues are still under debate including dose schemes personalization, selection of eligible patients, evaluation of treatment response and treatment sequencing.

Conclusion

PRRT is now recognized as an effective treatment strategy for well-differentiated SSTR-positive NETs with a very high disease control and overall limited toxicity. Further optimization of PRRT employment is warranted to further increase efficacy and reduce toxicity.

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Authors and Affiliations

  1. Nuclear Medicine, DIMES, Alma Mater Studiorum University of Bologna, Bologna, Italy

    Silvi Telo, Diletta Calabrò, Stefano Fanti & Valentina Ambrosini

  2. Nuclear Medicine Unit, Azienda USL-IRCCS Di Reggio Emilia, Reggio Nell’Emilia, Italy

    Angelina Filice & Annibale Versari

  3. IRCCS Azienda Ospedaliero-Universitaria of Bologna, Bologna, Italy

    Giuseppe Lamberti, Davide Campana, Stefano Fanti & Valentina Ambrosini

  4. Oncology, DIMES University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy

    Giuseppe Lamberti & Davide Campana

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  1. Silvi Telo
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Every author contributed equally to this manuscript.

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The authors, Silvi Telo MD, Giuseppe Lamberti MD, Davide Campana MD, PhD and Diletta Calabrò MD, have no conflicts of interest to disclose. Valentina Ambrosini reports personal fees from ESMIT, EANM and AAA outside the submitted work and is a member of ENETS advisory board, EANM Oncology and theranostic committee, ESMO faculty staff for NET and of the scientific board of ITANET. Stefano Fanti reports personal fees from ANMI, Astellas, Bayer, BlueEarth Diagnostics, GE Healthcare, Jenssen, Novartis, Sofie Biosciences, non-financial support from AAA, Bayer, GE Healthcare, Curium, Tema Sinergie, Sanofi, Telix, outside the submitted work. Angelina Filice reports personal fees from AAA, Novartis, Bayer and AstraZeneca outside the submitted work. Annibale Versari reports personal fees from Novartis and AAA outside the submitted work.

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Telo, S., Filice, A., Versari, A. et al. Peptide receptor radionuclide therapy for GEP-NET: consolidated knowledge and innovative applications. Clin Transl Imaging 9, 423–438 (2021). https://doi.org/10.1007/s40336-021-00443-y

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