title: Chemical Imaging of Platinum-Based Drugs and their Metabolites.
abstract: Platinum-based drugs (cisplatin, carboplatin, and oxaliplatin) are widely used therapeutic agents for cancer treatment. Even though the platinum (Pt)-drugs are routinely used clinically, a clear picture of their distribution within tumor tissues is lacking. The current methods to image the distribution of Pt drugs are limited and do not enable the discrimination of the drug from its metabolites. In this manuscript, we demonstrate a methodology that enables chemical imaging of a Pt drug and its metabolites simultaneously and specifically. Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry Imaging (MSI) is combined with an on-tissue chemical derivatization using diethyldithiocarbamate (DDTC). DDTC abstracts the Pt atom to generate ionizable complexes that can be imaged by MALDI MSI. We demonstrate that Pt drugs and their metabolites can be specifically imaged. This approach was successfully applied to map the penetration and metabolism of oxaliplatin in hyperthermic intraperitoneal chemotherapy (HIPEC)-like treated 3D colorectal tumor mimics. The distribution of cisplatin and carboplatin was mapped in additional 3D tumor mimics. We demonstrate that the approach can also be used to image the distribution of copper ions in cells. This method has the potential to be used to evaluate the penetration and distribution of a wide range of compounds.
authors.affiliation: Department of Chemistry and Biochemistry Harper Cancer Research Institute University of Notre Dame McCourtney Hall Notre Dame, IN 46556, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry Harper Cancer Research Institute University of Notre Dame McCourtney Hall Notre Dame, IN 46556, USA.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Hummon
mesh_terms: D016190:Carboplatin / Q000737:chemistry / Q000378:metabolism; D002853:Chromatography, Liquid; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D004050:Ditiocarb; D045325:HCT116 Cells; D006801:Humans; D006979:Hyperthermia, Induced; D021621:Imaging, Three-Dimensional; D055442:Metabolome; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000378:metabolism; D000077150:Oxaliplatin; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D010984:Platinum / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018874:Spheroids, Cellular / Q000473:pathology; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D003470:Culture Media; D009944:Organoplatinum Compounds; D004364:Pharmaceutical Preparations; D000077150:Oxaliplatin; D010984:Platinum; D004050:Ditiocarb; D016190:Carboplatin; D002945:Cisplatin