TY - JOUR T1 - First clinical results for radioligand therapy using the alpha emitter Ac-225-PSMA I&T in patients with end stage mCRPC JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 592 LP - 592 VL - 61 IS - supplement 1 AU - Mathias Zacherl AU - Franz Josef Gildehaus AU - Astrid Gosewisch AU - Guido Boening AU - Peter Bartenstein AU - Andrei Todica AU - Harun Ilhan Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/592.abstract N2 - 592Aim: Despite several agents are available for the therapy of metastatic castration resistant prostate cancer (mCRPC), end stage mCRPC after failure of approved therapy options remains challenging. Radioligand therapy (RLT) using β- and α-emitter labeled PSMA-inhibitors have been introduced with promising results. Here we present the first early clinical data for PSMA-directed α-therapy using Ac-225-PSMA I&T. Methods: 16 patients receiving Ac-225 PSMA I&T RLT between 08/18 and 12/19 have been included in this retrospective analysis. All but one patient had received second line antihormonal treatment using abiraterone and/or enzalutamide. 14 patients received prior chemotherapy. In 13 patients RLT using Lu-177-PSMA-ligands was performed prior to Ac-225 PSMA-ligandtherapy (median 2 cycles, rang 1-5). PSMA PET/CT was performed in all patients prior to Ac-225-PSMA I&T therapy to assess PSMA-expression in tumor lesions. Patients were treated at 7-8 weekly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) and blood cell count were measured every 2-3 weeks. We evaluated hematological and non-hematological side effects according to CTCAE 4.0 criteria and biochemical response. Results: A total of 32 cycles of Ac-225-PSMA I&T (median dose 7.9 MBq, range 6.7-8.2) were applied. 5 patients received 1 cycle, 7 patients 2 cycles, 3 patients 4 cycles and 1 patients 5 cycles. No acute toxicity was observed at the time of hospitalization. Baseline PSA was 337.6 ng/ml (range 13.4 - 1146). 4/16 patients had no follow-up and were excluded from the further study. 5/12 patients had a PSA-decline of more than 50%, 3/12 patients a decline of 40-50% and 2/12 patients a decline between 20-30%. Two patients had no PSA-decline at any time. Mild xerostomia (grade 1/2) was observed in 11 patients. Severe xerostomia (grade 3) was observed in 1 patient. No patient developed a new renal insufficiency. 6/12 patients had a grade 3-4 anemia. Conclusions: In this small cohort Ac-225-PSMA I&T RLT showed antitumor effect in end stage mCRPC even after failure of Lu-177 PSMA-ligand therapy in more than 40%. Grade 3/4 hematological side effects in 50% of patients and Grade 1-2 xerostomia in 11/12 patients indicate moderate tolerability in this heavily pretreated end stage patient group. These results are comparable to data for Ac225 PSMA-617 after failure of Lu-177 therapy. ER -