In vivo positron emission tomography (PET) imaging of mesenchymal-epithelial transition (MET) receptor.
In vivo positron emission tomography (PET) imaging of mesenchymal-epithelial transition (MET) receptor.
复制标题
DOI：
10.1021/jm900803q
复制
发表时间：
2010-01
影响因子：
7.3
通讯作者：
Chunying Wu;Zhe Tang;Weiwen Fan;Wenxia Zhu;Changning Wang;E. Somoza;N. Owino;Ruoshi Li;P. Ma;Yanming Wang
中科院分区：
文献类型：
--
作者：
Chunying Wu;Zhe Tang;Weiwen Fan;Wenxia Zhu;Changning Wang;E. Somoza;N. Owino;Ruoshi Li;P. Ma;Yanming Wang
我们报告了3-[3，5-二甲基-4-（4-[11 C]甲基哌嗪羰基）-1H-吡咯-2-基亚甲基]-2-氧代-2，3-二氢-1H-吲哚-5-磺酸（3-氯苯基）甲酰胺（命名为[11 C] SU 11274（[11 C]14））的放射合成和评价，用于正电子发射断层扫描（PET）对间充质-上皮转化（MET）受体的体内成像。在以9.7%的总产率在10个步骤中实现的前体（13）的合成之后，通过放射甲基化以5-10%的放射化学产率和超过95%的放射化学纯度获得[11 C]14。对于体内PET研究，使用MET阳性NCI-H1975和MET阴性NCI-H520细胞系建立了两种人肺癌异种移植物模型。定量[11 C]14-PET研究显示，NCI-H1975异种移植物中[11 C]14的肿瘤摄取显著高于NCI-H520异种移植物中的肿瘤摄取，这与来自相同动物的MET受体的相应免疫组织化学组织染色模式一致。这些研究表明，[11 C]14-PET是体内定量MET受体的适当成像标记物，可促进MET靶向癌症治疗药物临床开发中的疗效评价。
We report the radiosynthesis and evaluation of 3-[3,5-dimethyl-4-(4-[11C]methylpiperazinecarbonyl)-1H-pyrrol-2-ylmethylene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid (3-chlorophenyl)methylamide, termed [11C]SU11274 ([11C]14) for in vivo imaging of mesenchymal-epithelial transition (MET) receptor by positron emission tomography (PET). Following the synthesis of the precursor (13) that was achieved in 10 steps with a total yield of 9.7%, [11C]14 was obtained through radiomethylation in a range of 5-10% radiochemical yield and over 95% radiochemical purity. For in vivo PET studies, two human lung cancer xenograft models were established using MET-positive NCI-H1975 and MET-negative NCI-H520 cell lines. Quantitative [11C]14-PET studies showed that the tumor uptake of [11C]14 in the NCI-H1975 xenografts was significantly higher than that in the NCI-H520 xenografts, which is consistent with their corresponding immunohistochemical tissue staining patterns of MET receptors from the same animals. These studies demonstrated that [11C]14-PET is an appropriate imaging marker for quantification of MET receptor in vivo, which can facilitate efficacy evaluation in the clinical development of MET-targeted cancer therapeutics.