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Studies on Fluorinated Pyrimidines

XVII. Tissue Distribution of 5-Fluorouracil-2-C¹⁴ and 5-Fluoro-2'-deoxyuridine in Cancer Patients^*

Kanai Lal Mukherjee, A. R. Curreri, Manucher Javid and Charles Heidelberger

( McArdle Memorial Laboratory and Department of Surgery, University of Wisconsin, Madison, Wisconsin)

The uptake of radioactivity into the tumor and corresponding normal tissues after injections of 5-fluorouracil- (FU) and 5-fluoro-2'-deoxyuridine-2-C¹⁴ (FUDR) was studied in resected tissues of patients having different types of cancer. The specific activity of tumors varied considerably but was usually higher than the corresponding normal tissues, except in some cases of carcinoma of the colon, where the tumor and the intestinal mucosa had similar uptakes of the drugs. There was a rough correspondence between the amount of cellularity of the tumor and the drug uptake. Individual variations in the ability to convert the drugs into the nucleotides, the active forms of the drugs, were found in the tumors of the same tissue. There was a higher conversion of FUDR to nucleotides in carcinomas of the colon than in normal intestinal mucosa. Although the specific activities of some astrocytomas were high, the capacity of this type of tumor to convert the drug to the nucleotides was poor. Quantitative recovery of radioactivity in two segments of the intestine containing two different tumors, isolated surgically from the rest of the circulation, was possible after intra-arterial injections of labeled FU and FUDR.

^* This investigation was supported in part by Grant #T-157 from the American Cancer Society.

Fellow of the Damon Runyon Memorial Fund for Cancer Research.

American Cancer Society Professor of Oncology.

Received 6/11/62.