Comparison of short-lived high-LET alpha-emitting radionuclides lead-212 and bismuth-212 to low-LET X-rays on ovarian carcinoma

Abstract

We are investigating the potential use of short-lived alpha-emitting radionuclides for the treatment of ovarian carcinoma. These radionuclides transfer dense high ionizing linear energy (high LET) over a short path length without dependence upon cellular oxygen. The alpha-emitting radionuclides chosen were lead-212 and bismuth-212 which are readily available. The radiosensitivities of two ovarian carcinoma cell lines (OVC-1 and OVC-2) was greater with 212Pb and 212Bi than with X-ray therapy. D0, inversely related to the radiosensitivity, was 155 and 240 rads for OVC-1 and OVC-2, respectively. With 212Pb or 212Bi, the slope of the survival curves was steeper. The D0 was 75 and 70 rads after 212Pb and 85 and 95 rads after 212Bi treatment for OVC-1 and OVC-2, respectively. The relative biological effectiveness with alpha irradiation was two to four times greater than with X rays. Unlike low-LET irradiation (i.e., X rays and gamma emitters) the cells had no ability to accumulate or repair sublethal damage. From these experiments it is concluded that a greater therapeutic advantage may be gained with alpha-emitting radionuclides than X rays. Further development of these nuclides may provide for a new form of therapy.