Automated cGMP-compliant radiosynthesis of [ F]-(E)-PSS232 for brain PET imaging of metabotropic glutamate receptor subtype 5.

(E)-3-(Pyridin-2-yl ethynyl)cyclohex-2-enone O-(3-(2-[ F]-fluoroethoxy)propyl) oxime ([ F]-(E)-PSS232, [ F]2a) is a recently developed radiotracer that can be used to visualize metabotropic glutamate receptor subtype 5 (mGlu ) in vivo. The mGlu has become an attractive therapeutic and diagnostic target owing to its role in many neuropsychiatric disorders. Several carbon-11-labeled and fluorine-18-labeled radiotracers have been developed to measure mGlu receptor occupancy in the human brain. The radiotracer [ F]2a, which is used as an analogue for [ C]ABP688 ([ C]1) and has a longer physical half-life, is a selective radiotracer that exhibits high binding affinity for mGlu . Herein, we report the fully automated radiosynthesis of [ F]2a using a commercial GE TRACERlab™ FX- synthesizer for routine production and distribution to nearby satellite clinics. Nucleophilic substitution of the corresponding mesylate precursor with cyclotron-produced [ F]fluoride ion at 100°C in dimethyl sulfoxide (DMSO), followed by high-performance liquid chromatography (HPLC) purification and formulation, readily provided [ F]2a with a radiochemical yield of 40 ± 2% (decay corrected, n = 5) at the end of synthesis. Radiochemical purity for the [ F]-(E)-conformer was greater than 95%. Molar activity was determined to be 63.6 ± 9.6 GBq/μmol (n = 5), and the overall synthesis time was 70 minutes.