In vitro toxicity of (191)Pt-labeled cisplatin to a human cervical carcinoma cell line (ME-180).
OBJECTIVE
The aim of the present work was to examine the effect of (191)Pt-cisplatin, and to study the manner in which radiation and cisplatin interact, in a human cervical carcinoma cell line (ME-180).


METHODS
The cells were incubated for 1 hour with nonradioactive cisplatin or (191)Pt-cisplatin with specific activities in the range 48-167 MBq/mg. The surviving fraction of the cells after 7 days' growth was determined 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 (IC(50)) decreased with increasing specific activity of the (191)Pt-cisplatin. For the specific activities 0 (nonradioactive), 48, 89, 143, 157, and 167 MBq/mg, IC(50) 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 (synergistic) interaction between the radiotoxicity and chemotoxicity for specific activities over 100 MBq/mg.


CONCLUSIONS
The cytotoxic effect of cisplatin may be enhanced by labeling the drug with the radionuclide (191)Pt.
Areberg
J
J
Department of Radiation Physics, Malmö University Hospital, Malmö, Sweden. johan.areberg@rfa.mas.lu.se
Johnsson
A
A
Wennerberg
J
J
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010984:Platinum / Q000493:pharmacokinetics / Q000494:pharmacology*; D011868:Radioisotopes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011868:Radioisotopes; D010984:Platinum; D002945:Cisplatin