Background: Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA- 617 for therapy of metastatic castration-resistant prostate cancer have underlined the clinical potential of targeted alpha therapy. Objective and Conclusion: This review describes methods for the production of 225Ac and its daughter nuclide 213Bi and summarizes the current clinical experience with both alpha emitters with particular focus on recent studies of targeted alpha therapy of bladder cancer, brain tumors, neuroendocrine tumors and prostate cancer.

Purpose Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). A combination treatment using the high-energy ⁹⁰Y beta emitter for larger lesions and the lower energy ¹⁷⁷Lu for smaller lesions has been postulated in the literature.The aim of the study was to evaluate combined ⁹⁰Y/¹⁷⁷Lu-DOTATATE therapy in comparison to ⁹⁰Y-DOTATATE alone. Methods Fifty patients with disseminated NET were included in the study prospectively and divided into two groups: group A (n = 25) was treated with ⁹⁰Y-DOTATATE, whereas group B (n = 25) received the 1:1 ⁹⁰Y/¹⁷⁷Lu-DOTATATE. The administered activity was based on 3.7 GBq/m² body surface area in three to five cycles, with amino acid infusion for nephroprotection. Results The median overall survival time in group A was 26.2 months while in group B median survival was not reached. Overall survival was significantly higher in group B (p = 0.027). Median event-free survival time in group A was 21.4 months and in group B 29.4 months (p > 0.1). At the 12-month follow-up, comparison of group A vs group B showed stable disease (SD) in 13 vs 16 patients, disease regression (RD) in 5 vs 3 patients and disease progression (PD) in 3 vs 4 patients; 4 and 2 patients died, respectively. The 24-month follow-up results were SD in nine vs ten patients, RD in one patient vs none and PD in four patients in both groups; three and four patients died, respectively. Side effects were rare and mild. Conclusion The results indicate that therapy with tandem radioisotopes (⁹⁰Y/¹⁷⁷Lu-DOTATATE) provides longer overall survival than with a single radioisotope (⁹⁰Y-DOTATATE) and the safety of both methods is comparable.