SNMMI 2026
Alpha-emitting radiotherapy may offer new hope for resistant neuroendocrine cancers
Clinical Takeaway: Consider referral to specialized centers or clinical trials evaluating alpha-emitting PRRT for somatostatin receptor–positive neuroendocrine tumors after progression on conventional therapies.
Treatment options are limited for advanced neuroendocrine tumor patients who progress after standard therapies, highlighting the need for new targeted strategies.
A novel peptide receptor radionuclide therapy (PRRT) using the alpha-emitter ^225Ac-DOTA-LM3 demonstrated encouraging activity and manageable safety in patients with advanced, heavily pretreated grade 3 neuroendocrine tumors, according to data presented at SNMMI 2026.
In this real-world cohort of 20 patients, participants received either alpha-PRRT monotherapy (9 cycles) or a tandem regimen combining ^225Ac with ^177Lu (32 cycles total). These patients had heterogeneous tumor origins and had largely exhausted standard therapies, including prior beta-emitting PRRT.
Molecular imaging response revealed complete remission in 1 patient (5%), partial remission in 10 (50%), stable disease in 2 (10%), and progressive disease in 6 (30%). One patient died before post-treatment imaging. At a median follow-up of 7 months, 11 patients remained alive, while 9 had died, with a reported median survival of 18 months.
Treatment was generally well tolerated. Acute adverse events were mostly mild and self-limiting, such as nausea, while longer-term toxicities included anemia and thrombocytopenia, with occasional leukopenia.
“This cohort…showed a manageable safety profile and encouraging antitumor activity,” said lead author Elisabetta Perrone, MD, emphasizing the potential of alpha-emitting PRRT in patients with limited options. She noted that the short-range, high-energy radiation of alpha particles may improve tumor targeting while sparing surrounding tissues.
Investigators caution that ^225Ac-DOTA-LM3 remains investigational and currently limited to specialized centers. Larger prospective trials are needed to confirm efficacy, optimize dosing, and identify patients most likely to benefit.
Source: Perrone E, et al. Correlations between quantitative 68Ga-DOTATATE PET and 177Lu-DOTATATE dosimetry in patients with gastroenteropancreatic neuroendocrine tumors. Presented at: Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting; May 2026; Los Angeles, CA. Abstract 261577.