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.