Automated cGMP-compliant radiosynthesis of [18 F]-(E)-PSS232 for brain PET imaging of metabotropic glutamate receptor subtype 5.

Abstract

(E)-3-(Pyridin-2-yl ethynyl)cyclohex-2-enone O-(3-(2-[18 F]-fluoroethoxy)propyl) oxime ([18 F]-(E)-PSS232, [18 F]2a) is a recently developed radiotracer that can be used to visualize metabotropic glutamate receptor subtype 5 (mGlu5 ) in vivo. The mGlu5 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 mGlu5 receptor occupancy in the human brain. The radiotracer [18 F]2a, which is used as an analogue for [11 C]ABP688 ([11 C]1) and has a longer physical half-life, is a selective radiotracer that exhibits high binding affinity for mGlu5 . Herein, we report the fully automated radiosynthesis of [18 F]2a using a commercial GE TRACERlab™ FX-FN synthesizer for routine production and distribution to nearby satellite clinics. Nucleophilic substitution of the corresponding mesylate precursor with cyclotron-produced [18 F]fluoride ion at 100°C in dimethyl sulfoxide (DMSO), followed by high-performance liquid chromatography (HPLC) purification and formulation, readily provided [18 F]2a with a radiochemical yield of 40±2% (decay corrected, n=5) at the end of synthesis. Radiochemical purity for the [18 F]-(E)-conformer was greater than 95%. Molar activity was determined to be 63.6±9.6GBq/μmol (n=5), and the overall synthesis time was 70minutes.