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First Clinical Results for PSMA-Targeted α-Therapy Using 225 Ac-PSMA-I&T in Advanced-mCRPC Patients.

Authors :
Zacherl MJ
Gildehaus FJ
Mittlmeier L
Böning G
Gosewisch A
Wenter V
Unterrainer M
Schmidt-Hegemann N
Belka C
Kretschmer A
Casuscelli J
Stief CG
Unterrainer M
Bartenstein P
Todica A
Ilhan H
Source :
Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2021 May 10; Vol. 62 (5), pp. 669-674. Date of Electronic Publication: 2020 Oct 02.
Publication Year :
2021

Abstract

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 <superscript>225</superscript> Ac-PSMA imaging and therapy (I&T). Methods: Fourteen patients receiving <superscript>225</superscript> Ac-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 <superscript>177</superscript> Lu-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 <superscript>225</superscript> Ac-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 <superscript>177</superscript> Lu-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 <superscript>177</superscript> Lu-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 <superscript>225</superscript> Ac-PSMA-I&T showed a promising antitumor effect in advanced metastatic castration-resistant prostate cancer. These results are highly comparable to data on <superscript>225</superscript> Ac-PSMA-617 TAT.<br /> (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Details

Language :
English
ISSN :
1535-5667
Volume :
62
Issue :
5
Database :
MEDLINE
Journal :
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Publication Type :
Academic Journal
Accession number :
33008928
Full Text :
https://doi.org/10.2967/jnumed.120.251017