UBC Centre for Blood Research, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Cancer Res. 2010 Oct 1;70(19):7562-9. doi: 10.1158/0008-5472.CAN-10-1584. Epub 2010 Aug 20.
Matrix metalloproteinases (MMP), strongly associated pathogenic markers of cancer, have undergone extensive drug development programs. Marimastat, a noncovalent MMP inhibitor, was conjugated with FITC to label cellular metalloproteinase cancer targets in MDA-MB-231 cells in vitro. Punctate localization of active transmembrane MMP14 was observed. For molecular-targeted positron emission tomography imaging of syngeneic 67NR murine mammary carcinoma in vivo, marimastat was (18)F-labeled using a shelf-stable arylboronic ester conjugate as a captor for aqueous [(18)F]fluoride in a novel, rapid one-step reaction at ambient temperature. [(18)F]Marimastat-aryltrifluoroborate localized to the tumors, with labeling being blocked in control animals first loaded with >10-fold excess unlabeled marimastat. The labeled drug cleared primarily via the hepatobiliary and gastrointestinal tract, with multiple animals imaged in independent experiments, confirming the ease of this new labeling strategy.
基质金属蛋白酶（MMP）是与癌症密切相关的致病标志物，已经经历了广泛的药物开发计划。Marimastat 是一种非共价 MMP 抑制剂，它与 FITC 缀合以标记 MDA-MB-231 细胞中的细胞金属蛋白酶癌症靶点。观察到活性跨膜 MMP14 的点状定位。为了对体内同基因 67NR 鼠乳腺癌进行分子靶向正电子发射断层扫描成像，使用货架稳定的芳基硼酸酯缀合物作为水相[(18)F]氟化物的捕获物，在环境温度下以新颖的快速一步反应对 Marimastat 进行了 (18)F 标记。[(18)F]Marimastat-aryltrifluoroborate 定位于肿瘤，在先用 >10 倍过量未标记的 Marimastat 加载的对照动物中阻断标记。标记药物主要通过肝胆和胃肠道清除，在独立实验中对多个动物进行成像，证实了这种新的标记策略的简便性。
