Investigation of Side Effects During Radioactive (191Pt) Cisplatin Treatment in Wistar Rats

Abstract: Cisplatin is a cytostatic agent that has been used for more than 30 years in the treatment of a wide spectrum of tumours. The clinical use is limited by its side effects, primarily renal toxicity. An enhanced anti tumour effect has been demonstrated for radioactive (191Pt) cisplatin both in in vitro and in vivo models by our group. The purpose of the present study was to compare the side effects from radioactive cisplatin treatment and conventional cisplatin treatment, to see if a treatment gain would be achieved. Rats were given an i.p. bolus injection of 5 mg/kg 191Pt-cisplatin (85 MBq/mg, 113 MBq/mg, or 172 MBq/mg), 5 mg/kg conventional cisplatin, or physiological saline (controls). So far, 69 animals have been included in the study. To compare the different treatment groups the weight of the animals and plasma parameters, including creatinine, bilirubin, ALAT/ASAT and platelet count, was followed for six weeks after drug administration. A significant increase in creatinine levels was observed three days post administration of radioactive cisplatin as well as for conventional cisplatin treatment. There were no statistically significant difference in creatinine levels between the two cisplatin-treated groups, suggesting that the acute side effects occurring on the kidneys was caused by cisplatin only. No other significant differences were seen between plasma parameters. The weight of the cisplatin- and radioactive cisplatin-treated animals showed an initial decrease in weight from three days and for a week onward. Thereafter the weight gain followed the same pattern as for the control group. No significant difference was seen between the cisplatin-treated groups. The absorbed dose from 191Pt-cisplatin to rats was calculated for organs at risk. The highest absorbed dose was estimated to the kidneys (5.1-9.4 Gy) and the liver (1.3-2.3 Gy). In conclusion, no increase in toxicity for the group treated with radioactive cisplatin was seen, compared with the group given non-radioactive cisplatin.