Attempts to develop radioactive anticancer drugs

Abstract

Since 1953, attempts have been made to develop radioactive drugs. Preparations of tritiated menadiol sodium diphosphate (T-MNDP) of high specific activity showed a definite, though limited, but sometimes useful effect in the treatment of certain patients with advanced tumors, especially adenocarcinoms of the colon and of the pancreas and malignant melanoma of the skin. The next step was to use a much more effective isotope. 6- 125I-iodo-2-methyl-1,naphthoquinol bis (diammonium phosphate) - abbreviated 6- 125I-iodo-MNDP- has been synthesized, and in laboratory studies appears more promising. 125I provides radiations which behave predominantly like high LET radiation, despite the accompanying X and gamma radiations. The astatine analogue, 6- 211 At-astato-2rmethyl-1,4-naphthoquinol bis (disodium phosphate) has also been synthesized. Confirming and greatly extending the earlier findings with T-MNDP, n vitro experiments showed that 6- 125I-iodo-MNDP is concentrated selectively in the cells of some human malignant tumors by a factor of about 15 to 20 or more in relation to the cells of normal origin that were studied. Macrodosimetric considerations and comparison with clinical treatments with T-MNDP' suggest practical dosage. A typical treatment for a patient of body weight 70 kg with localized inoperable carcinoma of the colon could be 8 intravenous injections each of approximately 120mCi of 6- 125I-iodo-MNDP to a total of 0.97 Ci in 25 days. Risks of late carcinogenesis and leukemogenesis are calculated to be less than 1 %. Clinical indications are discussed briefly. Animal experiments are in progress and further preclinical studies are required.