[225Ac]Ac-PSMA-617 production method: Development of an efficient and reproducible radiolabelling process for establish a clinical routine production.

PURPOSE: Targeted Alpha Therapy show very promising clinical results in a cancer treatment and it is a superior therapeutic tool compared to chemotherapy and beta-radionuclide therapy. The use of alpha-emission, offers advantages over beta-emission due to the high linear energy transfer (LET) and the limited range in tissue. Ac-225 is an alpha emitter with a half-life of 9.92 days, which is an appropriate half-life for convenient treatment. 225Ac is introduced to tumor-targeting vectors through its complexation by a chelating moiety. On this basis, the aim of this study is to develop an 225Ac-PSMA-617 production method, assessment the efficiency and reliability of the radiosynthesis as a support for establish a clinical routine production for metastatic castration resistant prostate cancer treatment.

PROCEDURES:  PSMA-617 precursor was dissolved at 1 mM in metal-free water or DMSO 40% Different molar ratio of peptide, buffer solutions; 225AcCl3 activity and concentrations of stabilizing agent were utilized to perform a total of 21 syntheses. The complexation reaction was monitored by radio-TLC and radio-HPLC at time 0(t0’) and at 3 hours (t3h), when 221Fr and 213Bi were in Secular Equilibrium with 225Ac to establish with accuracy radiochemical purity (RCP) of radiopharmaceuticals. Stability was evaluated at 24 hours (t24h).

RESULTS: The method provided 225Ac-PSMA-617 in high radiochemical purity (>90%). The stability of [225Ac]Ac-PSMA-617 is instead influenced by the synthesis conditions.

CONCLUSIONS: the radiolabeling method employed in our experiments has demonstrated consistent reproducibility, allowing us to make a product that meets pharmaceutical-grade standards. This reproducibility is crucial as it ensures that the radiolabeled compounds maintain their integrity and efficacy throughout the production process. Greater difficulties were encountered in defining the optimal timing for quality controls, due to the unique physical properties of actinium.