Evaluation of carbon-11 labeled KF15372 and its ethyl and methyl derivatives as a potential CNS adenosine A1 receptor ligand.

We prepared [11C]KF15372 ([1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine, refs 10, 13) as well as its 11C-ethyl and 11C-methyl derivatives ([11C]EPDX and [11C]MPDX), and examined the potential of the three compounds as PET ligands for CNS adenosine A1 receptors. The three compounds had high affinity for the A1 receptors in vitro in the following order; [11C]EPDX > [11C]KF15372 > [11C]MPDX. In mice, the highest initial brain uptake was found in [11C]MPDX followed by [11C]EPDX and [11C]KF15372, but the level of [11C]MPDX decreased faster than those of the other two compounds. The uptake of each compound was decreased by carrier KF15372, but not by an A2A antagonist, indicating the selective affinity for the A1 receptors. Autoradiography with [11C]MPDX ex vivo demonstrated decreased A1 receptor binding in the superior colliculus of rats deprived of retino-collicular fibers by contralateral eye enucleation. These results show that three compounds have potential as PET ligands for CNS adenosine A1 receptors.