RT Journal Article SR Electronic T1 First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 669 OP 674 DO 10.2967/jnumed.120.251017 VO 62 IS 5 A1 Zacherl, Mathias Johannes A1 Gildehaus, Franz Josef A1 Mittlmeier, Lena A1 Böning, Guido A1 Gosewisch, Astrid A1 Wenter, Vera A1 Unterrainer, Marcus A1 Schmidt-Hegemann, Nina A1 Belka, Claus A1 Kretschmer, Alexander A1 Casuscelli, Jozefina A1 Stief, Christian G. A1 Unterrainer, Marcus A1 Bartenstein, Peter A1 Todica, Andrei A1 Ilhan, Harun YR 2021 UL http://jnm.snmjournals.org/content/62/5/669.abstract AB Treatment of advanced metastatic castration-resistant prostate cancer after failure of approved therapy options remains challenging. Prostate-specific membrane antigen (PSMA)–targeting β- and α-emitters have been introduced, with promising response rates. Here, we present the first—to our knowledge—clinical data for PSMA-targeted α-therapy (TAT) using 225Ac-PSMA imaging and therapy (I&T). Methods: Fourteen patients receiving 225Ac-PSMA-I&T were included in this retrospective analysis. Eleven of the 14 had prior second-line antiandrogen treatment with abiraterone or enzalutamide, prior chemotherapy, and prior 177Lu-PSMA treatment. Patients were treated at bimonthly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) was measured for response assessment. Hematologic and nonhematologic side effects were recorded according to the Common Terminology Criteria for Adverse Events, version 5.0. Results: Thirty-four cycles of 225Ac-PSMA-I&T were applied (median dose, 7.8 MBq; range, 6.0–8.5), with 1 cycle in 3 patients, 2 cycles in 7 patients, 4 cycles in 3 patients, and 5 cycles in 1 patient. No acute toxicity was observed during hospitalization. Baseline PSA was 112 ng/mL (range, 20.5–818 ng/mL). The best PSA response after TAT (a PSA decline ≥ 50%) was observed in 7 patients, and a PSA decline of any amount was observed in 11 patients. Three patients had no PSA decline at any time. A subgroup analysis of 11 patients with prior 177Lu-PSMA treatment showed any PSA decline in 8 patients and a decline of at least 50% in 5 patients. After TAT, grade 3 anemia was observed in 3 of the 14 patients, with 2 of them presenting with grade 2 anemia already at baseline. Grade 3 leukopenia was observed in 1 patient. Eight patients with preexisting xerostomia after 177Lu-PSMA showed no worsening after TAT. Newly diagnosed grade 1 or 2 xerostomia after TAT was observed in 5 patients. One patient reported no xerostomia at all. Conclusion: Our first clinical data for TAT using 225Ac-PSMA-I&T showed a promising antitumor effect in advanced metastatic castration-resistant prostate cancer. These results are highly comparable to data on 225Ac-PSMA-617 TAT.