BACKGROUND
The recent approval of radiopharmaceuticals for diagnosis and treatment of cancer is ushering nuclear medicine into a new era of theranostics, and alpha therapy using radiopharmaceuticals labeled with 225Ac is showing remarkable results in clinical trials. As such, reliable methods for the synthesis and quality control of 225Ac-radiopharmaceuticals are needed.
OBJECTIVE
225Ac-PSMA-617 is being used for targeted alpha therapy in patients with prostate cancer, and we aimed to synthesize the agent for preclinical use. However, technology transfer proved cumbersome owing to the paucity of information available on synthesizing and analyzing 225Ac-radiotherapeutics. To address this need, we describe a straightforward synthesis of 225Ac-PSMA-617 as well as suitable approaches for quality control analysis using standard equipment in a modern PET Center.
METHODS
PSMA-617 precursor was dissolved in 25 μL metal-free water (0.67 mg/mL), and combined with 500 μL 0.05M Tris buffer, pH 9. Actinium stock solution (~65 μCi in 15 µL) was added and the reaction was heated at 120˚C for 40-50 min. The reaction was cooled and 0.6 mL gentisic acid solution (4 mg/mL in 0.2 M NH4OAc) was added. To formulate the dose for injection, sterile saline, USP (8 mL) was added and the pH was adjusted by addition of 100 μL 0.05 M Tris buffer (pH 9) to achieve a final pH of ~7.2. The final solution was filtered using a 0.22 µm GV sterile filter into a sterile dose vial. Radiochemical purity was determined by radio-TLC (eluent: 50mM Sodium Citrate, pH 5) and plates were analyzed using an AR2000 scanner.
RESULTS
The method provided 225Ac-PSMA-617 in high radiochemical yield (57 ± 3 µCi, >99%) and radiochemical purity (98 ± 1%), formulated for preclinical studies (9 mL, pH = 7.2), n=3.
CONCLUSION
A straightforward synthesis of 225Ac-PSMA-617 is described that will facilitate production for (pre)clinical studies. The approach could also be applicable to the synthesis of other alpha radiotherapeutics incorporating 225Ac.