Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [(11)C]CB184 and [ (11)C]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [ (11)C](R)-PK11195.
Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [(11)C]CB184 and [ (11)C]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [ (11)C](R)-PK11195.
复制标题
DOI：
10.1007/s12149-015-0948-8
复制
发表时间：
2015-05
影响因子：
2.6
通讯作者：
Toyama H
中科院分区：
文献类型：
--
作者：
Hatano K;Sekimata K;Yamada T;Abe J;Ito K;Ogawa M;Magata Y;Toyohara J;Ishiwata K;Biggio G;Serra M;Laquintana V;Denora N;Latrofa A;Trapani G;Liso G;Suzuki H;Sawada M;Nomura M;Toyama H
我们报道了两种碳 11 标记的咪唑并吡啶 TSPO 配体 [11C]CB184 和 [11C]CB190 的合成，用于炎症过程以及神经退行性变、缺血或脑肿瘤的 PET 成像。将这些化合物的生物分布与[11C]CB148 和[11C](R)-PK11195 进行比较。使用[ 11 C]三氟甲磺酸甲酯可以容易地制备在芳环上具有11 C-甲氧基的[ 11 C]CB184和[ 11 C]CB190。用正常小鼠检查了化合物的生物分布和代谢。使用 6-羟基多巴胺治疗的大鼠作为神经变性模型进行了动物 PET 研究，以正确评估放射性配体确定神经炎症过程的可行性。 [11C]CB184 和 [11C]CB190 通过使用[11C]三氟甲磺酸甲酯对相应的去甲基前体进行 O-甲基化获得，放射化学产率为 73%（衰减校正）。使用正常小鼠和病变大鼠进行了作为 TSPO 放射性配体的体内验证。在小鼠中，[11C]CB184 比 [11C]CB190 显示出更多的摄取和特异性结合。代谢研究表明，静脉注射[11C]CB184和[11C]CB190后30分钟，血浆中的放射性分别保持不变36%和25%。在使用大鼠进行的 PET 研究中，静脉注射后，大脑病变侧的摄取量明显高于对侧。注射[11C]CB184或[11C](R)-PK11195。间接洛根图分析揭示了两侧之间的分布体积比（DVR），这可能表明与病变相关的 TSPO 结合升高。 [11C](R)-PK11195 的 DVR 为 1.15 ± 0.10，[11C]CB184 的 DVR 为 1.15 ± 0.09。 [11C]CB184 和 [11C](R)-PK11195 检测神经炎症活动的灵敏度相似。
We report synthesis of two carbon-11 labeled imidazopyridines TSPO ligands, [11C]CB184 and [11C]CB190, for PET imaging of inflammatory process along with neurodegeneration, ischemia or brain tumor. Biodistribution of these compounds was compared with that of [11C]CB148 and [11C](R)-PK11195. Both [11C]CB184 and [11C]CB190 having 11C-methoxyl group on an aromatic ring were readily prepared using [11C]methyl triflate. Biodistribution and metabolism of the compounds were examined with normal mice. An animal PET study using 6-hydroxydopamine treated rats as a model of neurodegeneration was pursued for proper estimation of feasibility of the radioligands to determine neuroinflammation process. [11C]CB184 and [11C]CB190 were obtained via O-methylation of corresponding desmethyl precursor using [11C]methyl triflate in radiochemical yield of 73 % (decay-corrected). In vivo validation as a TSPO radioligand was carried out using normal mice and lesioned rats. In mice, [11C]CB184 showed more uptake and specific binding than [11C]CB190. Metabolism studies showed that 36 % and 25 % of radioactivity in plasma remained unchanged 30 min after intravenous injection of [11C]CB184 and [11C]CB190, respectively. In the PET study using rats, lesioned side of the brain showed significantly higher uptake than contralateral side after i.v. injection of either [11C]CB184 or [11C](R)-PK11195. Indirect Logan plot analysis revealed distribution volume ratio (DVR) between the two sides which might indicate lesion-related elevation of TSPO binding. The DVR was 1.15 ± 0.10 for [11C](R)-PK11195 and was 1.15 ± 0.09 for [11C]CB184. The sensitivity to detect neuroinflammation activity was similar for [11C]CB184 and [11C](R)-PK11195.