Automated synthesis of 18F-labeled ligands for pre- and postsynaptic PET imaging of the dopaminergic system using IBA Synthera modules

Objectives Positron emission tomography for non invasive in vivo-diagnosis of DAT- and D2/D3-like receptor functions is considered to be a valuable tool for differential diagnosis and early detection of Parkinsons disease. Aim of this study was to provide the fully automated synthesis of 18F-Fallypride, 18F-DMFP (both D2 receptor antagonists) and 18F-PR04.MZ, a new selective and high affine DAT ligand for PET imaging, using the IBA Synthera platform.

Methods 18F-Fluoride was produced by 18O(p,n)18F-reaction (Cyclone 18/9 IBA) and transferred to a spare vial. 18F-PR04.MZ, 18F-Fallypride and 18F-DMFP were labeled by direct nucleophilic fluorination of corresponding mesyl and tosyl precursors. Purification was reached by HPLC, solid phase extraction and sterile filtration and different steps were optimized for adaptation to the Synthera platform. IFPs were purchased from ABX and used without any modifications.

Results Starting activities of 9-35 GBq were used for labeling and 18F-PR04.MZ, 18F-Fallypride and 18F-DMFP were obtained in high radiochemical puritiy (>95 %) and high RCYs of 42, 36 and 34 %, respectively. Total synthesis time for all ligands was in the range of 55-65 minutes and specific activities were in the range of 47-480 GBq/μmol. Final products were analyzed and in accordance with all regulations by the European Pharmacopoea.

Conclusions The full, automated synthesis of different 18F-labeled ligands for pre- and postsynaptic imaging of the dopaminergic system could be applied to IBA cassette modules under GMP conditions.