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The Direct Mapping of the Uptake of Platinum Anticancer Agents in Individual Human Ovarian Adenocarcinoma Cells Using a Hard X-ray Microprobe¹

Experimental Facilities Division, Argonne National Laboratory, Argonne, Illinois 60439 [P. I., B. L., Z. C., W. Y., D. L., A. P. J. S.]; Department of Biochemistry, La Trobe University, VIC 3083, Australia [T. T., D. R. P.]; Pharmacology and Developmental Therapeutics Unit, Peter MacCallum Cancer Institute, VIC 3002, Australia [T. T., L. K. W., S. R.]; School of Physics, University of Melbourne, VIC 3052, Australia [M. C.]; Department of Chemistry, Monash University, VIC 3168, Australia [G. B. D.]; and Physics Division, Australian Nuclear Science and Technology Organisation, NSW 2234, Australia [A. P. J. S.]

Uptake of platinum-based anticancer compounds into individual human ovarian andenocarcinoma cells was measured using an X-ray microprobe. The uptake of cisplatin, a platinum-based compound, in drug-resistant cells is decreased by 50% after 24 h, compared with the uptake of the drug in nonresistant cells over the same time period. The Pt103 derivative of the drug, in contrast, showed an increased uptake by an order of magnitude in resistant cells over the same time period. Increased uptake appears to allow Pt103 to overcome the resistance mechanism developed by the cell. This work additionally shows that the X-ray microprobe is able to directly quantify Pt drug uptake on a subcellular level and can measure the mass of Pt down to a detectable limit of 20 attograms of Pt (2 x 10^-17 grams or 6 x 10⁴ Pt atoms) in 1 s. Such exquisite elemental sensitivity combined with high spatial resolution paves the way for quantitative submicron three-dimensional mapping of elemental distributions within individual cells.

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