Quantitative imaging microscopy for the sensitive detection of administered metal containing drugs in single cells and tissue slices--a demonstration using platinum based chemotherapeutic agent

Abstract

We described the use of Nuclear microscopy (microbeam PIXE) for the quantitative micron scale analysis of platinum based chemotherapeutic agents in individual cell and tissue slices. We demonstrate that microbeam 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 cells in a time- and dose-dependent fashion. Additionally, the technique can quantitatively image therapeutic levels of cisplatin and cisplatin analogs including cis-diammine[1,1-cyclobutanedicarboxylato] platinum (II) (carboplatin) in tissues from an animal model. This quantitative imaging 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 toxic response and cell function.