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

作者：Park Jun Young; Son Jeongmin; Yun Mijin; Ametamey Simon M.; Chun Joong-Hyun^*

来源：Journal of Labelled Compounds and Radiopharmaceuticals, 2018, 61(1): 30-37.

DOI：10.1002/jlcr.3566

• [F-18]-(E)-PSS232
• automation
• fluorine-18
• mGlu(5)
• PET imaging
• radiopharmaceutical

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

• 出版日期2018-1