In vitro toxicity of Pt-191-labeled cisplatin to a human cervical carcinoma cell line (ME-180)

Purpose: The aim of the present work was to examine the effect of Pt-191-ci splatin, and to study the manner in which radiation and cisplatin interact, in a human cervical carcinoma cell line (ME-180). Methods and Materials: The cells were incubated for 1 hour with nonradioact ive cisplatin or Pt-191-cisplatin with specific activities in the range 48- 167 MBq/mg, The surviving fraction of the cells after 7 days' growth was de termined with a nonclonogenic tetrazolium-based (MTT) assay. The uptake of platinum into the cell and the amount of platinum bound to DNA was measured . Results: The 50% inhibition concentration (IC50) decreased with increasing specific activity of the Pt-191-cisplatin, For the specific activities 0 (n onradioactive), 48, 89, 143, 157, and 167 MBq/mg, IC50 was found to be 3.24 +/- 0.08, 2.77 +/- 0.55, 2.17 +/- 0.34, 1.15 +/- 0.04, 1.02 +/- 0.03, and 0.76 +/- 0.13 respectively. Isobologram analysis showed a supra-additive (s ynergistic) interaction between the radiotoxicity and chemotoxicity for spe cific activities over 100 MBq/mg. Conclusion: The cytotoxic effect of cisplatin may be enhanced by labeling t he drug with the radionuclide Pt-191. (C) 2000 Elsevier Science Inc.