作者:Scott M. Apana、Lawrence W. Anderson、Marc S. Berridge
DOI:10.1002/jlcr.1746
日期:——
SN-38 (7-ethyl-10-hydroxy camptothecin) is a topoisomerase I inhibitor that is the active chemotherapeutic agent of irinotecan, indicated for colon cancer. Because the rate of response to irinotecan treatment is low, it is of interest to have a prognostic indicator to identify and more selectively treat those who are likely to respond to treatment. We have therefore prepared SN-38 labeled with carbon-11. SN-38 was prepared by radical oxidation of 3-[11C]propionaldehyde and subsequent radical addition of the ethyl fragment to 10-hydroxycamptothecin. Labeled propionaldehyde was prepared by reaction of methyl iodide with 2-lithiomethyl-1,3-dioxolane. Overall chemical yield was 34% from carbon dioxide. The murine biodistribution and radiation dosimetry of [11C]SN-38 was measured by PET scanning in preparation for initial human studies. Biodistribution was fairly uniform except for hepatobiliary and urinary excretion. Copyright © 2010 John Wiley & Sons, Ltd.
SN-38(7-乙基-10-羟基喜树碱)是一种拓扑异构酶I抑制剂,是伊立替康的活性化疗药物,适用于结肠癌。由于对伊立替康治疗的反应率较低,因此寻找一个预后指标,以便识别和更有选择性地治疗可能对治疗有反应的患者,具有重要意义。因此,我们制备了标记了碳-11的SN-38。SN-38通过对3-[11C]丙醛的自由基氧化反应及随后将乙基片段自由基加到10-羟基喜树碱上制备而成。标记的丙醛是通过甲基碘与2-锂甲基-1,3-二恶烷反应制备的。总体化学收率为34%,来源于二氧化碳。通过正电子发射断层扫描(PET)测量了[11C]SN-38的小鼠生物分布和辐射剂量,以为首次人类研究做准备。生物分布相对均匀,除了肝胆和尿液排泄。版权所有 © 2010 John Wiley & Sons, Ltd.