GMP-compliant fully automated single-step radiosynthesis of [¹⁸F]PSMA-1007 using SPE cartridge purification

Objectives: In recent years radiofluorinated ligands targeting the prostate-specific membrane antigen (PSMA) have been reported [1]. These ligands are possible candidates for large scale production. The aim of the present study was the optimization of an automated GMP-compliant single-step radiosynthesis of [¹⁸F]PSMA-1007 [2]. Materials and methods After azeotropic drying of [¹⁸F]fluoride using tetrabutylammonium hydrogen carbonate solution as base, the fully automated radiosynthesis of [¹⁸F]PSMA-1007 has been conducted on several commercially available automated radiosynthesizers (GE TRACERlab FX FN,MX and FASTLab, ORA Neptis Plug and RS, IBA Synthera) using 1.0 to 2.0 mg of precursor in DMSO for 10 minutes at 85 °C. Therefore a radiolabelling precursor for direct nucleophilic substitution using trimethylammonium as leaving group has been developed. The crude reaction mixture was taken up in 5% EtOH solution and trapped on pre-conditioned sequenced SPE cartridges (Chromafix PS-H+ and Chromafix C18ec, Macherey-Nagel). After rinsing with 5% EtOH solution, the purified product was eluted from the cartridges with 30% EtOH solution and diluted with PBS solution. After sterile filtration, quality control for [¹⁸F]PSMA-1007 was performed according to specifications set in compliance with current pharmacopoeias. Results [¹⁸F]PSMA-1007 could be obtained in radiochemical yields ranging from 30-80% and radiochemical purities > 95 % in a total synthesis time of < 60 min in dependence of the type of radiosynthesizer (GE TRACERlab FX FN,MX and FASTLab, ORA Neptis Plug and RS, IBA Synthera ) used. No radiolysis of the product has been observed up to 8 hours after final batch formulation (40 GBq in 20 mL PBS solution). Conclusion A GMP-compliant radiosynthesis and quality control of [¹⁸F]PSMA-1007 using direct radiofluorination and a simple purification procedure have been established on a wide range of commercially available radiosynthesizers (GE TRACERlab FX FN,MX and FASTLab, ORA Neptis Plug and RS, IBA Synthera). The product is obtained in good radiochemical yields with satisfying batch productions covering the daily clinical demand in a university hospital. The product quality of all batches was fulfilling current pharmaceutical standards. Prospective clinical trials are initiated. Research Support [1] Giesel F et al. J Nucl Med. 2017 Dec 21. pii: jnumed.117.204669. doi: 10.2967/jnumed.117.204669. [Epub ahead of print] [2] Cardinale J et al., Pharmaceuticals (Basel) 2017 Sep 27;10(4). pii: E77. doi: 10.3390/ph10040077.