Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis
Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis
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DOI：
10.1016/j.bmcl.2006.07.045
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发表时间：
2006-10-01
影响因子：
2.7
通讯作者：
Mach, Robert H.
中科院分区：
文献类型：
--
作者：
Zhou, Dong;Chu, Wenhua;Mach, Robert H.
合成了一种非肽基的吲哚磺酰胺类似物WC-II-89，并测定了其对重组人caspase-3和其他caspase的抑制作用。该化合物对caspase-3和-7有较强的抑制作用，对caspase-1、-6和-8有较高的选择性。[F-18]WC-II-89是通过甲磺酸盐前体的亲核取代反应合成的，产率和放化纯度都很高。用[F-18]WC-II-89进行的生物分布研究表明，与对照组相比，环己亚胺处理的大鼠肝脏和脾的摄取更高，这是一种细胞凋亡的动物模型。Western印迹分析证实，在环己亚胺处理的动物的肝和脾中存在活化的caspase-3。MicroPET成像研究显示，与未处理的对照组相比，经放线菌亚胺处理的大鼠肝脏对放射性示踪剂的摄取较高。这些数据表明，[F-18]WC-II-89是一种潜在的放射性示踪剂，用于显示发生细胞凋亡的组织中caspase-3的激活情况。(C)2006爱思唯尔有限公司。保留所有权利。
A non-peptide-based isatin sulfonamide analog, WC-II-89, was synthesized and its inhibition toward recombinant human caspase-3 and other caspases was determined. This compound showed high potency for inhibiting caspase-3 and -7, and high selectivity against caspases-1, -6, and -8. [F-18]WC-II-89 was synthesized via a nucleophilic substitution of the corresponding mesylate precursor in high yield and radiochemical purity. Biodistribution studies using [F-18]WC-II-89 revealed higher uptake in liver and spleen of cycloheximide-treated rats, an animal model of apoptosis, relative to control animals. Western blot analysis confirmed the presence of activated caspase-3 in the liver and spleen of cycloheximide-treated animals. MicroPET imaging studies revealed a high uptake of the radiotracer in the liver of a cycloheximide-treated rat relative to the untreated control. These data suggest that [F-18]WC-II-89 is a potential radiotracer for imaging caspase-3 activation in tissues undergoing apoptosis. (c) 2006 Elsevier Ltd. All rights reserved.