选择性腺苷A2A拮抗剂[11C]KF17837的合成与初步评价

Synthesis and preliminary evaluation of [11C]KF17837, a selective adenosine A2A antagonist.

作者信息

Ishiwata K, Noguchi J, Toyama H, Sakiyama Y, Koike N, Ishii S, Oda K, Endo K, Suzuki F, Senda M

机构信息

Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo.

出版信息

Appl Radiat Isot. 1996 May-Jun;47(5-6):507-11. doi: 10.1016/0969-8043(95)00295-2.

DOI:10.1016/0969-8043(95)00295-2

PMID:8673072

Abstract

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.

摘要

一种11C标记的选择性腺苷A2A拮抗剂，(E)-8-(3,4-二甲氧基苯乙烯基)-1,3-二丙基-7-[11C]-甲基黄嘌呤([11C]KF17837)，通过(E)-8-(3,4-二甲氧基苯乙烯基)-1,3-二丙基黄嘌呤与[11C]碘甲烷反应制备，衰变校正后的放射化学产率为19-50%，放射化学纯度>99%，比活度为17-100 GBq/μmol，制备时间为20-25分钟。在小鼠中，静脉注射后5分钟心肌摄取最高(13.4% ID/g)，并随时间逐渐降低。心肌特异性摄取通过γ相机显像。在脑区，富含A2A受体的纹状体中的放射性水平高于皮质和小脑。大鼠纹状体的特异性摄取通过正电子发射断层扫描(PET)得到明确证实。这些结果表明，[11C]KF17837是一种潜在的PET放射性配体，可用于绘制心脏和脑中的腺苷A2A受体图谱。