Optimisation and automation of [18F]PSMA-1007 production, a next generation PET ligand for prostate carcinoma, using a GE FASTlab 2. (2018)

670 Objectives: Our aim was to optimise a one-step radiosynthesis of [18F]PSMA-1007 on a GE FASTlab 2 radiochemistry module using disposable cassettes. Methods: We optimised the 18F-nucleophilic substitution reactions on the trimethyl ammonium pyridinium trifluoroacetate and acetate derivatives of the unprotected PSMA peptide, based on radiochemical reaction conditions reported previously1. Radiosynthesis was carried out on a FASTlab 2, using developer cassettes and an in-house developed synthesis sequence. 18F-fluoride (~140 GBq) was produced on a GE PETtrace cyclotron employing a 30 min beam at 100 μA. Optimisation studies included the use of dry DMSO, DMF and a DMF:t-butanol (20:80) mixture; different bases including tetrabutylammonium hydrogen carbonate (TBAHCO3), cesium hydrogen carbonate, potassium oxalate and potassium carbonate and different temperatures. The influence of aqueous 0.075M TBAHCO3vs. 0.14M TBAHCO3 in acetonitrile:water on the [18F]PSMA-1007 reaction yield and purity were also studied. The reaction mixture was purified by trapping and elution with 20% ethanol-water through PSH+ and C-18 cartridges in series. Stabilisation of [18F]PSMA-1007 was achieved using sodium ascorbate or sodium thiosulfate. Results: The optimum 18F-radiolabelling conditions were obtained when using 0.14 M TBAHCO3 acetonitrile:water (1:4) as eluent and DMF as the reaction solvent at 95oC for 10 min using 2 mg of the unprotected trimethylammonium pyridinium acetate derivative. The trifluoroacetate and the acetate counterions gave similar radiochemical yields (35-45%). However, the acetate salt resulted in slightly higher radiochemical purity (97-98% vs 95-96%). Aqueous TBAHCO3 (0.075M) eluent also gave high radiochemical purity (>97%), but in a lower radiochemical yield (20-30%). Potassium oxalate in DMF and CsHCO3 also provided [18F]PSMA-1007, but in reduced radiochemical yield (10-20%). Since the reaction uses the unprotected trimethylammonium pyridinium PSMA precursor which involves the deprotonation of five carboxylic acid groups, the concentration and number of base equivalents to the precursor is crucial. We attributed the superior radiochemical yield of [18F]PSMA-1007 to the larger base:precursor ratio and more efficient drying of the 0.14 M TBAHCO3 acetonitrile:water solution. In-line SPE purification, followed by elution with 20% ethanol-water and formulation with phosphate buffer:sodium ascorbate, gave [18F]PSMA-1007 in 30-45% RCY, stable for at least 5 hours post synthesis. Conclusion: [18F]PSMA-1007 can be synthesised in good radiochemical yield (30-45%), non-decay corrected, on a FASTlab 2 using disposable cassettes, in 98% radiochemical purity within 35 min. The synthesis resulted in 30-50 GBq of product from a 30 minute irradiation that will allow it to be used for multiple clinical PET-CT studies. Acknowledgement: We would like to thank Dr Oliver Neels and ABX for their helpful discussions. Reference: J. Cardinale et al. Procedures for the GMP-Compliant Production and Quality Control of [18F]PSMA-1007 - A Next Generation Radiofluorinated Tracer for the Detection of Prostate Cancer. Doi:10.20944/preprints201708.0057v1