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基质辅助激光解吸/电离成像质谱法分析加热腹腔内化疗(HIPEC)样处理大鼠肾脏中奥沙利铂衍生物。

Matrix-assisted laser desorption/ionization imaging mass spectrometry of oxaliplatin derivatives in heated intraoperative chemotherapy (HIPEC)-like treated rat kidney.

机构信息

IRCM, Institut de Recherche en Cancérologie de Montpellier, F-34298 Montpellier, France.

出版信息

Rapid Commun Mass Spectrom. 2010 Feb;24(4):415-21. doi: 10.1002/rcm.4408.

Abstract

Oxaliplatin [1,2-diaminocyclohexane (dach)-Pt complex] is a platinum anticancer drug which is mainly used in the treatment of advanced colorectal cancer, particularly in Heated Intraoperative Chemotherapy (HIPEC) for the treatment of colorectal peritoneal carcinomatosis. In order to better understand the penetration of oxaliplatin in treated tissues we performed a direct imaging of tissue sections from HIPEC-like treated rat kidney using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. This procedure allowed the detection and localization of oxaliplatin and its metabolites, the monocysteine and monomethionine complexes, in kidney sections. Specifically, oxaliplatin and its metabolites were localized exclusively in the kidney cortex, suggesting that it did not penetrate deeply into the organ. Based on these results, an imaging analysis of human tumors collected after HIPEC is currently in progress to assess the distribution of oxaliplatin and/or metabolites with the aim of defining clinical conditions to improve drug penetration.

摘要

奥沙利铂[1,2-二氨基环己烷(dach)-Pt 配合物]是一种铂类抗癌药物,主要用于治疗晚期结直肠癌,特别是在腹腔热灌注化疗(HIPEC)中治疗结直肠腹膜转移癌。为了更好地了解奥沙利铂在治疗组织中的渗透情况,我们使用基质辅助激光解吸/电离(MALDI)质谱法对类似 HIPEC 治疗的大鼠肾脏组织切片进行了直接成像。该程序允许在肾脏切片中检测和定位奥沙利铂及其代谢物,即单半胱氨酸和单甲硫氨酸配合物。具体来说,奥沙利铂及其代谢物仅定位在肾脏皮质中,表明其未深入渗透到器官中。基于这些结果,目前正在对 HIPEC 后收集的人类肿瘤进行成像分析,以评估奥沙利铂和/或代谢物的分布,目的是确定改善药物渗透的临床条件。

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