In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma

Indian J Nucl Med. 2021 Apr-Jun;36(2):114-119. doi: 10.4103/ijnm.ijnm_200_20. Epub 2021 Jun 21.

Abstract

Purpose: Ac-225 labeled with prostate-specific membrane antigen (PSMA-617), a transmembrane glycoprotein which is highly expressed in prostate carcinoma cells, is presently being considered a promising agent of targeted alpha therapy for the treatment of patients suffering from metastatic castration-resistant prostate cancer. In the present study, we report an optimized protocol for the preparation of therapeutic dose of Ac-225 PSMA-617 with high yield and radiochemical purity (RCP).

Methods: Ac-225 PSMA-617 was prepared by adding the peptidic precursor-PSMA-617 (molar ratios, Ac-225: PSMA-617 = 30:1) in 1 ml ascorbate buffer to Ac-225 and heating the reaction mixture at 90°C for 25 min to obtain the radiopeptide with high RCP and yield. The radiolabeled peptide was administered in patients who met the eligibility criteria and posttherapy assessment was done.

Results: Ten batches of Ac-225 PSMA-617 were prepared following this protocol. The radiopeptide was obtained with an adequate yield of 85%-87% and RCP of 97%-99%.

Conclusion: The current protocol allows single-step, successful, routine inhouse radiolabeling of Ac-225 with PSMA-617 with high yield and RCP.

Keywords: Ac-225 prostate-specific membrane antigen-617; labeling; prostate cancer; radiochemical purity; targeted alpha therapy.