Distribution of Irinotecan in Liver and a Human Tumor Xenograft Model byTissue Imaging Mass Spectrometry
6 Oct 2008
Purpose: To determine irinotecan metabolites and their distribution in human tumors directly from tissue by MALDI LTQ XL Imaging MS. To establish MALDI ion trap technology as ideally suited for direct tissue analysis of drugs in tissue.
Methods: Nude mice with transplanted human head and neck tumors were treated with either irinotecan, methylselenocysteine (MSC), both drugs in combination, or nontreated (control). Frozen tumors and livers were sliced to ~12 µm thick and thaw-mounted on to non-conductive glass slides. Irinotecan metabolites were investigated by Single Reaction Monitoring or CRM with an LTQ XL coupled to a MALDI source.
Results: Metabolites previously identified in human urine samples were detected directly off tissue in all irinotecan treated tissues and those with both irinotecan plus MSC. SN-38-G, a known irinotecan metabolite, seems more uniformly distributed in the tumor treated with irinotecan plus MSC.