Evaluation of carbon-11-labeled KF17837: a potential CNS adenosine A2a receptor ligand.
The 11C-labeled KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxa nthine) was evaluated as a PET ligand for mapping adenosine A2a receptors in the central nervous system (CNS).


METHODS
The regional brain distribution of [11C]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 [11C]KF17837 and the effect of carrier KF17837 was visualized by autoradiography. Imaging of the monkey brain with [11C]KF17837 was performed by PET.


RESULTS
In mice, a high uptake of [11C]KF17837 was found in the striatum in which A2a receptors were highly enriched. The uptake was decreased by co-injection of carrier KF17837 or a xanthine-type A2a antagonist CSC but not by nonxanthine-type A2a antagonists ZM 241385 or SCH 58261, or an A1 antagonist KF15372. In the rat brain, [11C]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.


CONCLUSIONS
Carbon-11-KF17837 binds to adenosine A2a 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 A2a antagonists.
Noguchi
J
J
Positron Medical Center and Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Gerontology, Japan.
Ishiwata
K
K
Wakabayashi
S
S
Nariai
T
T
Shumiya
S
S
Ishii
S
S
Toyama
H
H
Endo
K
K
Suzuki
F
F
Senda
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000032:analysis; D013237:Stereoisomerism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014970:Xanthines / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D018047:Receptors, Purinergic P1; D014970:Xanthines; C081198:KF 17837