Carbon-11-labeled KF21213: a highly selective ligand for mapping CNS adenosine A2A receptors with positron emission tomography

In vivo assessment of the adenosine A(2A) receptors localized in the striatum with positron emission tomography (PET) may offers us a new diagnostic tool for neurological disorders. We evaluated the potential of [7-methyl-(11)C](E)-8-(2,3-dimethyl-4-methoxystyryl)-1, 3,7-trimethylxanthine ([(11)C]KF21213) as a PET ligand for mapping adenosine A(2A) receptors in the central nervous system. KF21213 showed a high affinity for the adenosine A(2A) receptors in vitro (Ki = 3.0 nM) and a very low affinity for the A(1) receptors (Ki > 10,000 nM). In mice, the striatal uptake of [(11)C]KF21213 increased for the first 15 min and then gradually decreased, whereas the uptake in the reference regions such as the cortex and cerebellum rapidly decreased. The uptake ratio of striatum to cortex and striatum to cerebellum increased to 8.6 and 10.5, respectively, at 60 min postinjection. The striatal uptake was significantly blocked by co-injection of carrier KF21213 or each of three other A(2A) antagonists, but not by co-injection of A(1) antagonist. The specific uptake was not detected in the cortex or in the cerebellum. Ex vivo autoradiography and PET clearly visualized adenosine A(2A) receptors in the rat striatum. [(11)C]KF21213 was the most selective tracer for mapping adenosine A(2A) in the central nervous system by PET among the tracers proposed to date.