Single‐cell measurement of the uptake, intratumoral distribution and cell cycle effects of cisplatin using mass cytometry

Although of fundamental importance to the treatment of cancer patients, the quantitative study of drug distribution and action in vivo at the single cell level is challenging. We used the recently‐developed technique of mass cytometry to measure cisplatin uptake into individual tumor cells (Pt atoms/cell), combined with measurement of the rate of IdU incorporation into DNA (I127 atoms/cell/min) and tumor hypoxia identified by the 2‐nitroimidazole EF5 in cisplatin‐treated BxPC‐3 and ME‐180 xenografts. Pt levels of 105 to 106 atoms/cell were obtained following a single cisplatin treatment using clinically relevant doses. Cisplatin caused cell cycle arrest in a dose‐ and time‐dependent manner that paralleled effects in vitro, and it readily penetrated into hypoxic tumor regions. Similar levels of Pt/cell were found in xenografts treated with oxaliplatin. Mass cytometry offers the unique capability to study the cellular uptake and anticancer effects of platinum‐containing drugs at the single cell level in animal models, and it has the potential for application to samples obtained from cancer patients during treatment. What's new? The ways in which tumors develop resistance to drugs are complex, and it would be useful if drug distribution and action could be studied in vivo at the single‐cell level. In this report, the authors used a technique called mass cytometry in mice to measure the number of molecules of cisplatin and IdU taken into individual tumor cells per minute. They also used a probe molecule called EF5, which showed that cisplatin easily spreads through hypoxic regions of tumors. These results demonstrate the potential for precise measurement of drug distribution and pharmacodynamic effects in vivo.