Evaluation of carbon-11-labeled KF17837:: A potential CNS adenosine A2a receptor ligand

The C-11-labeled KF17837 ([7-methyl-C-11](E)-8-(3,4-dimethoxy-styryl)-1, 3-dipropyl-7-methylxanthine) was evaluated as a PET ligand for mapping adenosine A(2a) receptors in the central nervous system (CNS). Methods: The regional brain distribution of [C-11]KF17837 and the effect of adenosine antagonists on the distribution were measured in mice by the tissue sampling method. In rats, the regional brain uptake of [C-11]KF17837 and the effect of carrier KF17837 was visualized by autoradiography. Imaging of the monkey brain with [C-11]KF17837 was performed by PET, Results: In mice, a high uptake of [C-11]KF17837 was found in the striatum in which A,, receptors were highly enriched. The uptake was decreased by co-injection of carrier KF17837 or a xanthine-type A(2a), antagonist CSC but not by nonxanthine-type A(2a) antagonists ZM 241385 or SCH 58261, or an A(1) antagonist KF15372, In the rat brain, [C-11]KF17837 was accumulated higher in the striatum than in other brain regions, and the uptake was blocked by co-injection of carrier KF17837. In a monkey PET study, a high striatal uptake of radioactivity was observed. Conclusion: Carbon-11-KF17837 binds to adenosine A(2a), receptors in the striatum. However, the presence of an unknown but specific binding site for xanthine-type compounds also was suggested in the other brain regions. The results also suggested that the in vivo receptor-binding sites of xanthine-type ligands are slightly different from those of nonxanthine-type A(2a) antagonists.