REVIEW article
Front. Nucl. Med.
Sec. Radiopharmacy and Radiochemistry
Volume 5 - 2025 | doi: 10.3389/fnume.2025.1655419
This article is part of the Research TopicPeptide Radiotheranostics: Pioneering the Future of Targeted Cancer TreatmentsView all articles
Targeted Radionuclide Therapy and Diagnostic Imaging of SSTR Positive Neuroendocrine Tumors: A Clinical Update in the New Decade
Provisionally accepted
- Department of Nuclear Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, Knoxville, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms characterized by their overexpression of somatostatin receptors (SSTRs), which can be utilized for peptide receptor radionuclide therapy. This review provides a comprehensive update on the clinical trials of radiolabeled SSTR-targeting radiopharmaceuticals since 2020, with a focus on somatostatin receptor agonists and antagonists radiolabeled with 68 Ga, 18 F, 99m Tc, 177 Lu, 161 Tb, 212 Pb, 67 Cu, and 225 Ac. Head-to-head clinical trials demonstrate that radiolabeled SSTR antagonists such as [ 68 Ga]Ga-DOTA-JR11 and [ 68 Ga]Ga-DOTA-LM3 offer improved lesion detection and tumor-to-background ratios (particularly in liver metastases) compared to radiolabeled agonists like [ 68 Ga]Ga-DOTA-TOC and [ 64 Cu]Cu-DOTA-TATE. Additionally, 18 F-labeled agents offer logistical and dosimetric advantages over 68 Ga, due to 18 F's longer half-life and cyclotron production, allowing for delayed imaging and increased availability to a wider range of patients. Emerging targeted alpha therapy agents, including [ 225 Ac]Ac-DOTA-TATE, show promising results in treating disease resistant to conventional therapies due to the high linear energy transfer of alpha particles, which leads to improved localized cytotoxicity. Collectively, these developments support a shift toward more precise, receptor-specific theragnostics, emphasizing the need for further head-to-head clinical trials and integration of dosimetry-driven, personalized treatment planning in the management of NETs.
Keywords: Neuroendocrine Tumors, Radiopharmaceuticals, peptide receptor radionuclide therapy, Theragnostics, Diagnostic Imaging
Received: 27 Jun 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Haugh, Sanwick and Chaple. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ivis Francis Chaple, Department of Nuclear Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, Knoxville, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.