Synthesis and preliminary evaluation of [11C]KF17837, a selective adenosine A2A antagonist.
An 11C-labeled selective adenosine A2A antagonist, (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-[11C]-methylxanthine ([11C]KF17837), was prepared by reaction of (E)-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine and [11C]methyl iodide with decay-corrected radiochemical yield of 19-50%, radiochemical purity of > 99%, sp. act. of 17-100 GBq/mumol and preparation time of 20-25 min. In mice, the myocardium showed the highest (13.4% ID/g) at 5 min after i.v. injection, which decreased gradually with time. The specific myocardial uptake was visualized by gamma-camera. In the brain region the radioactivity level was higher in the A2A receptors-rich striatum than in the cortex and cerebellum. The specific striatal uptake in rats was clearly demonstrated by PET. These results have shown that [11C]KF17837 is a potential PET radioligand for mapping the adenosine A2A receptors in the heart and brain.
Ishiwata
K
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo.
Noguchi
J
J
Toyama
H
H
Sakiyama
Y
Y
Koike
N
N
Ishii
S
S
Oda
K
K
Endo
K
K
Suzuki
F
F
Senda
M
M
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014970:Xanthines / Q000138:chemical synthesis* / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C081198:KF 17837