New GABA B 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 GABA B agonist 1a, suggesting that the radiotracer brain uptake is partially mediated by GABA B receptors. The presented data demonstrate a feasibility of imaging of GABA B receptors in rodents and justify further development of GABA B PET tracers with improved specific binding and greater blood-brain barrier permeability.
- GABAB receptor
- blood-brain barrier permeability