F-18 LABELED BENZAMIDES FOR STUDYING THE DOPAMINE-D(2) RECEPTOR WITH POSITRON EMISSION TOMOGRAPHY
F-18 LABELED BENZAMIDES FOR STUDYING THE DOPAMINE-D(2) RECEPTOR WITH POSITRON EMISSION TOMOGRAPHY
复制标题
DOI：
10.1021/jm00075a028
复制
发表时间：
1993-11-12
影响因子：
7.3
通讯作者：
EHRENKAUFER, RL
中科院分区：
文献类型：
--
作者：
MACH, RH;LUEDTKE, RR;EHRENKAUFER, RL
制备了两个系列的（N-苄基哌啶-4-基）-和（9-氮杂双环[3.3.1]壬-3 β-基）苯甲酰胺，并使用体外结合试验来测量这些化合物对多巴胺D2、多巴胺D3、5-羟色胺5-HT 2和α 2-肾上腺素能受体的亲和力。这些研究的结果表明化合物23、26 b和34具有D2（和可能的D3）受体的体内研究所需的选择性。23、26 b和34的F-18-标记的类似物通过相应的脱苄基前体与[F-18]-4-氟苄基碘的N-烷基化制备。初步的体内研究表明，[F-18]-23和[F-18]-26 b是在正电子发射断层扫描成像研究中进一步评价的合适候选物。[F-18]-34从非多巴胺能区域洗脱的缓慢速率及其相对较高的亲脂性表明，由于高水平的非特异性结合，该化合物可能不适合用于成像研究。
Two series of (N-benzylpiperidin-4-yl)- and (9-azabicyclo[3.3.1]nonan-3beta-yl)benzamides were prepared, and in vitro binding assays were used to measure the affinity of these compounds for dopamine D2, dopamine D3, serotonin 5-HT2, and alpha2-adrenergic receptors. The results of these studies indicated compounds 23, 26b, and 34 have the selectivity needed for in vivo studies of the D2 (and possibly D3) receptors. F-18-Labeled analogues of 23, 26b and 34 were prepared by N-alkylation of the corresponding desbenzyl precursors with [F-18]-4-fluorobenzyl iodide. Preliminary in vivo studies demonstrated that [F-18]-23 and [F-18]-26b are suitable candidates for further evaluation in positron emission tomography imaging studies. The slow rate of washout of [F-18]-34 from nondopaminergic regions and its comparatively high lipophilicity indicates that this compound may not be suitable for imaging studies because of a high level of nonspecific binding.