Automated radiosynthesis of ¹⁸F-PSMA-11 for large scale routine use

Objectives: Various ¹⁸F-labeled urea-based radiotracers for PET imaging of PSMA have been developed that allow direct labeling of the peptides via aluminum-fluoride (Al¹⁸F) chelation. Despite the existence of successful labeling protocols, not a single method has been reported that allows the production of large amounts of ¹⁸F-PSMA-11, sufficient for routine application in a clinical setting. The aim of this work was to develop a reproducible automated radiosynthesis for large scale batch production of high quality ¹⁸F-PSMA-11.

Methods: A customized Synthra RNplus module (Synthra GmBh) was used to synthetize ¹⁸F-PSMA-11 from commercially available PSMA-11 (ABX) by aluminum-fluoride (Al¹⁸F) chelation. The process was based on previously described manual procedures and optimized/altered to account for the specific issues arising from working with high amounts of freshly produced ¹⁸F-fluoride (i.e. radionuclidic impurities, radiolysis,⋯). After production, quality control was performed on all batches and the stability of ¹⁸F-PSMA-11 in the final formulation was assessed by means of HPLC and TLC.

Results: The radiofluorinated compound ¹⁸F-PSMA-11 was successfully synthetized within 35 minutes in an average yield of 13.5 +/- 3.2 % (not corrected for decay) and with a radiochemical purity exceeding 95% in all cases. All produced batches passed the quality control tests required by the European Pharmacopeia for radiotracers to be injected into humans. We have successfully demonstrated the synthesis of several batches of ¹⁸F-PSMA-11, starting with approximately 0.1 TBq of radioactivity and obtained up to 16.5 GBq (non-decay-corrected) of ¹⁸F-PSMA-11. The specific activity of was estimated to be 64 +/- 18 GBq/μmol. Loss of radiolabel was greatly reduced by optimization of the reaction parameters as defluorination of ¹⁸F-PSMA-11 is suspected to be related to the formation of an unstable isomer, similar to the different isomer described for ⁶⁸Ga-PSMA-11. Strict control of reaction parameters almost quantitatively removes the undesired isomer, leading to a compound that meets the radiopharmaceutical requirements over a time frame of at least 4 hours.

Conclusion: The optimized synthesis of ¹⁸F-PSMA-11 using a Synthra RNplus allows for large scale production of high quality ¹⁸F-PSMA-11, suitable for routine human application in a clinical setting. As many doses can now efficiently be prepared in a single production- cycle, widespread use of the tracer is possible. Research Support: Nothing to declare