Automated cGMP‐compliant radiosynthesis of [18F]‐(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‐[18F]‐fluoroethoxy)propyl) oxime ([18F]‐(E)‐PSS232, [18F]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 [18F]2a, which is used as an analogue for [11C]ABP688 ([11C]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 [18F]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 [18F]fluoride ion at 100°C in dimethyl sulfoxide (DMSO), followed by high‐performance liquid chromatography (HPLC) purification and formulation, readily provided [18F]2a with a radiochemical yield of 40 ± 2% (decay corrected, n = 5) at the end of synthesis. Radiochemical purity for the [18F]‐(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.