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Systemic administration of hypoxia-selective ⁶⁴Cu-diacetyl-bis(N⁴-methylthiosemicarbazone) (⁶⁴Cu-ATSM) has increased significantly the survival time of hamsters bearing human GW39 colon cancer tumors. Radiotherapy experiments were performed in animals bearing either 7-day-old (0.5–1.0 g) or 15-day-old (1.5–2.0 g) tumors. Studies compared animals treated with a single dose of 0, 4, 6, 7, 8, or 10 mCi of ⁶⁴Cu-ATSM (1 Ci = 37 GBq) with or without the vasodilator hydralazine. A multiple dose regimen of 3 × 4 mCi at 72-h intervals was studied also. Single doses of >6 mCi of ⁶⁴Cu-ATSM and the dose-fractionation protocol significantly increased the survival time of the hamsters compared with controls. The highest dose, 10 mCi of ⁶⁴Cu-ATSM, increased survival to 135 days in 50% of animals bearing 7-day-old tumors, 6-fold longer than control animals' survival (20 days), with only transient …