Therapeutic application of iodine-125 labeled iododeoxyuridine in an early ascites tumour model.

In its decay, iodine-125 emits cascades of Auger electrons with subcellular ranges and leaves a highly charged tellurium-125 product. When iodine-125 is incorporated into DNA as the thymidine analog 125I-UdR, the localized deposition of such energy has been shown to be extremely radiotoxic. This report presents the results of quantitative investigations into the therapeutic efficacy of 125I-UdR in an early ascites murine tumour model. An ovarian embryonal cell carcinoma has been maintained by serial intraperitoneal transplantation. Challenge doses of 10(4)-10(6) cells were used. Four divided doses of 125I-UdR were administered starting 24 h after tumour cell inoculation; the interval between doses was 4 or 12 h. Therapeutic efficacy was demonstrated by prolonged median and increased absolute survivals of treated animals. Divided doses were more effective than single doses, and antineoplastic activity was related to fractionation. The degree of cell killing with a given fractionation scheme was constant over the range of 10(4)-10(6) cells, and total doses of 50-100 muCi resulted in a 2-3 log killing of tumour cells (1-0.1% cell survival). Therapy with 125I-UdR affords a promising new approach to the treatment of cancer. The therapeutic potential of iodine-125 and other radionuclides whose decay results in a highly localized deposition of energy merits further investigation.