Synthesis and Evaluation of a New 18 F-Labeled Radiotracer for Studying the GABA B Receptor in the Mouse Brain.

New GABAB agonists, fluoropyridyl ether analogues of baclofen, have been synthesized as potential PET radiotracers. The compound with highest inhibition binding affinity as well as greatest agonist response, ( R)-4-amino-3-(4-chloro-3-((2-fluoropyridin-4-yl)methoxy)phenyl)butanoic acid (1b), was radiolabeled with 18 F with good radiochemical yield, high radiochemical purity, and high molar radioactivity. The regional brain distribution of the radiolabeled ( R)-4-amino-3-(4-chloro-3-((2-[18 F]fluoropyridin-4-yl)methoxy)phenyl)butanoic acid, [18 F]1b, was studied in CD-1 male mice. The study demonstrated that [18 F]1b enters the mouse brain (1% ID/g tissue). The accumulation of [18 F]1b in the mouse brain was inhibited (35%) by preinjection of GABAB agonist 1a, suggesting that the radiotracer brain uptake is partially mediated by GABAB receptors. The presented data demonstrate a feasibility of imaging of GABAB receptors in rodents and justify further development of GABAB PET tracers with improved specific binding and greater blood-brain barrier permeability.