PRRT using somatostatin-based peptides is now a well-established treatment for neuroendocrine tumors, with new trials expanding its use to higher-grade tumors and combination strategies.
FDA-approved 2017Lutathera became the first FDA-approved peptide receptor radionuclide therapy based on the NETTER-1 trial, establishing PRRT as standard care for neuroendocrine tumors
What the researchers found
PRRT is now incorporated into major oncology guidelines based on NETTER-1 trial results. The NETTER-2 trial may expand first-line use to G2/G3 NET patients. Dual tracer PET/CT using both FDG and Ga-68 DOTA-SSA could improve patient selection and prognostication. Combination therapies with other agents may enhance efficacy. Somatostatin receptor antagonists and alternative isotopes are being explored as next-generation options.
Why it matters
PRRT is the quintessential example of peptide-targeted therapy — using the body's own receptor system to guide radiation directly to tumor cells. Its success has validated the concept of 'theranostics' (using the same peptide for both imaging and therapy) and opened doors for similar approaches in other cancers.
The numbers in context
PRRT was first performed over 30 years ago. Lutathera was FDA-approved in 2017 based on the NETTER-1 trial for G1/G2 NET patients.
How the study worked
Comprehensive narrative review of clinical trials, treatment strategies, and emerging approaches in PRRT for neuroendocrine tumors.
Who was studied
Patients with neuroendocrine tumors treated with PRRT
What this study cannot tell us
Narrative review without systematic methodology. Some emerging strategies discussed are still in early clinical development. Not all NET patients have sufficient somatostatin receptor expression for PRRT. Long-term side effects of repeated PRRT cycles need more study.
How to read the evidence
Rated strong: comprehensive review summarizing phase 3 RCT evidence (NETTER-1, NETTER-2) and established clinical guidelines for PRRT.
When this study was published
Published in 2024. Covers the full history of PRRT plus the latest developments including NETTER-2 and emerging strategies.
The bigger picture
PRRT exemplifies the theranostic concept: the same somatostatin-targeting peptide diagnoses the tumor (PET imaging) and treats it (radiation therapy). This model is now being replicated for other cancers using different peptide-receptor pairs.
Questions still open
- Will somatostatin receptor antagonists outperform agonists for PRRT?
- Can combination PRRT strategies further improve outcomes for difficult-to-treat NETs?
- Will the theranostic model extend successfully to common cancers beyond NETs?
Common questions
What is peptide receptor radionuclide therapy?
Who is eligible for PRRT?
Read the original research
Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives.
Seminars in nuclear medicine, 54(4), 557-569
Citation
Santo, Giulia; Di Santo, Gianpaolo; Virgolini, Irene. (2024). Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives.. Seminars in nuclear medicine, 54(4), 557-569. https://doi.org/10.1053/j.semnuclmed.2024.02.002