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Incorporation of iododeoxyuridine into neoplastic DNA: A fraudulent magic bullet?

Fourteen patients received 5‐iodo‐2 ‐deoxyuridine (IdUrd) before surgery for placement of a hepatic arterial catheter. Biopsy specimens were obtained at the time of surgery and the incorporation of IdUrd into DNA in tumor and normal hepatic tissue was measured by high‐performance liquid chromatography and used as an index of drug selectivity. Over a 3‐day intravenous infusion of IdUrd at 1,000 mg/m2/day, substitution for thymidine in tumor DNA averaged 3.1%. Normal hepatic DNA contained <1% substitution by IdUrd. Arterial delivery of IdUrd increased levels in DNA, whereas modulation with fluorodeoxyuridine produced mixed results. In six patients, flow cytometric analysis showed that the tumor contained a median of 32% tumor cells that had incorporated IdUrd in 3 days, corresponding to a potential doubling time of only 10 days. Thymidylate synthetase activity in tumors was 20‐fold greater than in normal liver tissue, whereas thymidine kinase activity was two‐fold greater in tumors. These pharmacological studies encourage further clinical trials of IdUrd as a cytotoxic agent or radiosensitizer.