A new radiopharmaceutical agent for tumor scanning.

Abstract

Several quinol diphosphates and related compounds have been tried extensively as chemical radiosensitizers by Mitchell and his group (1–4). Tetrasodium 2-methyl-l ∶4-naphthoquinol diphosphate (trade-name, Synkavit by Roche Products, Ltd.) was found the most promising in this respect in animal experiments and clinical trials (4). They also reported on the use of tritium-labeled Synkavit as a radiotherapeutic agent in the treatment of cancer (4). It is believed that the radiosensitizing and the radiotherapeutic effects of this chemical are by virtue of its property of selective concentration in malignant tumors (4). Marrian et al. labeled this substance with radioactive iodine and radioactive bromine and studied the distribution of the halogenated compound in rats with Walker carcinoma (5). The radioactive label was found to be too unstable to be of any therapeutic value, but they observed, for at least half an hour after the injection, a significant concentration of the radioisotope in the tumor. On the basis of these reports, iodinated Synkavit appears to have little value in radiotherapy because the concentration in the tumor is short-lived, but we thought it could still be useful in tumor-scanning. Our procedure for iodination of this chemical and our initial results in animal experiments are reported in this communication. Iodination of Synkavit: At the Isotope Division of the Atomic Energy Establishment Trombay, 50 mg of 2-methyl-l: 4-naphthoquinol-diphosphate sodium salt was purified by precipitation with absolute ethyl alcohol. The residue was separated by centrifugation, dried by evaporation, and then dissolved in 2.0 ml of water. Forty to fifty millicuries of NaI131 (100 mc/ml), free of carrier and reducing agent, was mixed with 0.1 ml of 0.01N KI solution, 0.3 ml of 0.005N KIO3 solution, and a few drops of 2N H2SO4 to liberate the iodine in solution. To this solution, a few drops of pH 5–6 (1M) sodium acetate buffer were added, followed by the solution of Synkavit. The mixture was kept cooled in ice with occasional stirring for two hours, at the end of which time the unreacted iodine was extracted with CCI4. A few drops of carrier (0.1N) KI and the requisite quantity of KIO3 were added, followed by dil. H2SO4 to liberate the iodine which is again drawn off. This procedure was repeated until the extracted iodine showed no activity due to I131. The aqueous phase containing the radioiodinated Synkavit was aerated to remove traces of CCI4 and adjusted for isotonicity. Animals: Scanning of the tumor was attempted in 17 mice with spontaneous mammary adenocarcinoma (C3H/J strain), 3 mice with transplanted adenocarcinoma (A, Strong strain) and 6 mice with transplanted fibrosarcoma (Swiss strain). The animals were selected for experiments only when the tumor was distinctly visible. In all cases, the nature of the lesion was confirmed by histological examination after the death of the animal.