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

Background

Targeted Alpha Therapy shows very promising clinical results in a cancer treatment and it should be comparable or better than chemotherapy and β-radionuclide therapy, in terms of efficacy and toxicity. The use of α-emission offers advantages over β-emission due to the high linear energy transfer and the limited range in tissue. Actinium-225 is an α-emitter with a half-life of 9.92 days, which is an appropriate half-life for convenient treatment. Actinium-225 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]Ac-PSMA 617 production method, to assess the efficiency and reliability of the radiosynthesis as a support for establish a clinical routine production for metastatic castration resistant prostate cancer treatment.

Results

different radiolabeling conditions and different reaction times have been used and compared. The best radiochemical yields (> 95%) were obtained when the peptide was dissolved in water and it was used at quantity of 100 µg in gentisic buffer, without stabilizing agent. The reaction was conducted at 97 °C and no significant change in labeling yield was observed when the time reaction increased. This condition ensures an adequate stability at 24 h around 90%.

Conclusions

the radiolabeling method employed in our experiments has demonstrated consistent reproducibility, enabling us to produce a radiopharmaceutical that meets pharmaceutical-grade standards. Greater difficulties occurred in defining the optimal procedures for quality controls, due to the unique physical properties of actinium. Efforts were made to standardize the quality control methods in accordance with pharmacopoeia standards; however, the methods’ feasibility is still uncertain.