Peptide Receptor Radionuclide Therapy (PRRT) Using Actinium-225- and Ac-225/Lutetium-177-Labeled (TANDEM) Somatostatin Receptor Antagonist DOTA-LM3 in Patients with Neuroendocrine Neoplasm: A Retrospective Study Concerning Safety and Survival

Peptide Receptor Radionuclide Therapy (PRRT) offers radiomolecular precision medicine for somatostatin receptor (SSTR)-positive advanced neuroendocrine neoplasms (NEN). In cases resistant to Lutetium-177-labeled DOTATATE or DOTATOC PRRT, alpha-therapy with Actinium-225 labeled with SSTR antagonists like DOTA-LM3 can be a notable therapeutic option. This retrospective study aimed to assess [225Ac]Ac-DOTA-LM3 safety in advanced NEN patients (as monotherapy and with Lutetium-177 as TANDEM), survival, and follow-up duration. Thirty-five patients received a total of 57 [225Ac]Ac-DOTA-LM3 cycles (March 2022–September 2024): 24 monotherapies and 33 TANDEM therapies. The pancreas was the most common primary site (n = 19). PRRT-related toxicity was assessed, focusing on hematological, renal, and hepatic toxicity (Common Terminology Criteria for Adverse Events—CTCAE v5.0). Therapy was generally well tolerated, with mostly mild acute adverse events (primarily nausea, n = 8). Some new grade 3/4 long-term adverse events were reported after treatment: anemia grade 3 (n = 2), leukocytopenia grade 4 (n = 1), absolute neutrophil count reduction grade 3 (n = 1), thrombocytopenia grade 3 (n = 7), acute myeloid leukemia (n = 1), nephrotoxicity grade 3 (n = 2), and hepatotoxicity grade 3 (n = 2). During follow-up, 13 patients died (survival range 5–30 months); 22 patients were alive (follow-up range 1–18 months). Our retrospective analysis shows that [225Ac]Ac-DOTA-LM3 PRRT is relatively safe concerning acute and long-term toxicity and bears promising survival outcomes in patients progressing after [177Lu]Lu-DOTATATE or [177Lu]Lu-DOTATOC PRRT.