QUANTITATIVE IMAGING MICROSCOPY FOR THE SENSITIVE DETECTION OF ADMINISTERED METAL-CONTAINING DRUGS IN SINGLE CELLS AND TISSUE-SLICES - A DEMONSTRATION USING PLATINUM-BASED CHEMOTHERAPEUTIC-AGENTS

We describe the use of Nuclear microscopy (microbeam PIXE) for the qua ntitative micron scale analysis of platinum based chemotherapeutic age nts in individual cells and tissue slices. We demonstrate that microbe am PIXE has the sensitivity and accuracy to quantitatively measure the uptake of the chemotherapeutic agent cis-diamminedichloroplatinum(II) (cisplatin) and monitor other endogenous metal contents in single cel ls in a time- and dose-dependent fashion. Additionally, the technique can quantitatively image therapeutic levels of cisplatin and cisplatin analogs including diammine[1,1-cyclobutanedicarboxylato]platinum(II) (carboplatin) in tissues from an animal model. This quantitative imagi ng microscopy has general application for the sensitive measurement of metal containing drugs/compounds at the cellular level and allows the study of cellular distribution and mechanism of action related to tox ic response and cell function. (C) 1998 Elsevier Science B.V. All righ ts reserved.