RT Journal Article SR Electronic T1 First clinical results for PSMA targeted alpha 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 jnumed.120.251017 DO 10.2967/jnumed.120.251017 A1 Mathias Johannes Zacherl A1 Franz Josef Gildehaus A1 Lena Mittlmeier A1 Guido Boening A1 Astrid Gosewisch A1 Vera Wenter A1 Nina-Sophie Schmidt-Hegemann A1 Claus Belka A1 Alexander Kretschmer A1 Jozefina Casuscelli A1 Christian G. Stief A1 Marcus Unterrainer A1 Peter Bartenstein A1 Andrei Todica A1 Harun Ilhan YR 2020 UL http://jnm.snmjournals.org/content/early/2020/10/02/jnumed.120.251017.abstract AB Background: Treatment of advanced metastatic castration resistant prostate cancer (mCRPC) 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 clinical data for PSMA targeted α-therapy (TAT) using 225Ac-PSMA-I&T. Methods: 18 patients receiving 225Ac-PSMA-I&T have been included in this retrospective analysis. 15/18 had prior second line antiandrogen treatment with abiraterone and/or enzalutamide, 15/18 prior chemotherapy and 13/18 prior 177Lu-PSMA treatment. Patients were treated at bi-monthly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) was measured for response assessment. Hematological and non-hematological side effects were recorded according to CTCAE v5.0 criteria. Results: 38 cycles of 225Ac-PSMA-I&T were applied (median dose 7.8 MBq, range 6.0 – 8.5) with 1 cycle in 7/18, 2 cycles in 7/18, 4 cycles in 3/18 and 5 cycles in 1 patient. No acute toxicity was observed during hospitalization. Baseline PSA was 176 ng/ml (range 13.4 - 1146). 4/18 patients were excluded due to incomplete follow-up. Best PSA response after TAT with a PSA decline ≥ 50% was oberved in 7/14 patients. Any PSA decline was seen in 11/14 patients. 3 patients had no PSA decline at any time. A subgroup analysis of 11 patients with prior 177Lu-177-PSMA treatment showed any PSA decline in 8/11 and a PSA decline ≥ 50% in 5/11 patients. Therapy related adverse events included deteroriation from grade 1 anemia baseline to grade 2 and grade 3 anemia in 4/14 and 1/14 patients after TAT, respectively. Grade 3 leukopenia was observed in 1 patient. Newly diagnosed grade 1 and grade 2 xerostomia was observed in 2 and 3 patients, respectively. However, including pre-existing xerostomia after prior 177Lu-177 PSMA, 8/14 patients had grade 1 and 5/14 grade 2 xerostomia after TAT. No further grade 3/4 hematological or non-hematological toxicities were observed. Conclusion: Our first clinical data for TAT using 225Ac-PSMA-I&T showed promising antitumor effect in advanced mCRPC even after failure of prior 177Lu-PSMA treatment with tolerable side effects. These results are highly comparable to data on 225Ac-PSMA-617 TAT.