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Peptide receptor radionuclide therapy (PRRT) with 177 LuLu-DOTATATE is an established treatment option for progressive, gastroenteropancreatic neuroendocrine tumors (GEP-NETs). While this approach provides durable disease control in many patients, objective response rates remain modest. Targeted alpha therapy (TAT) has emerged as a potential next-generation strategy by delivering higher linear energy transfer (LET) radiation, which may enhance tumor cytotoxicity while limiting off-target damage. Preclinical studies using alpha-emitters, including 212 Pb, 213 Bi and 225 Ac, with more limited evidence available for 211 At, have suggested antitumor activity and manageable toxicity profiles. Early clinical trials and first-in-human studies report preliminary signals of activity and acceptable short-term safety profiles in selected patient populations. However, these findings remain based on small, heterogeneous cohorts with limited follow-up. Ongoing clinical trials will be essential to better define the efficacy, safety and optimal positioning of alpha therapy within current treatment algorithms. This review summarizes current clinical indications for PRRT in GEP-NETs and discusses emerging strategies to optimize its efficacy, with a particular focus on the development of alpha-based radionuclide therapies.
Esnault et al. (Mon,) studied this question.