TY - JOUR T1 - First Clinical Results for PSMA-Targeted α-Therapy Using <sup>225</sup>Ac-PSMA-I&amp;T in Advanced-mCRPC Patients JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 669 LP - 674 DO - 10.2967/jnumed.120.251017 VL - 62 IS - 5 AU - Mathias Johannes Zacherl AU - Franz Josef Gildehaus AU - Lena Mittlmeier AU - Guido Böning AU - Astrid Gosewisch AU - Vera Wenter AU - Marcus Unterrainer AU - Nina Schmidt-Hegemann AU - Claus Belka AU - Alexander Kretschmer AU - Jozefina Casuscelli AU - Christian G. Stief AU - Marcus Unterrainer AU - Peter Bartenstein AU - Andrei Todica AU - Harun Ilhan Y1 - 2021/05/10 UR - http://jnm.snmjournals.org/content/62/5/669.abstract N2 - 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&amp;T). Methods: Fourteen patients receiving 225Ac-PSMA-I&amp;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&amp;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&amp;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. ER -