Neocarzinostatin (NCS) is an acidic protein with proven antitumor activity in experimental animals and is now in clinical trial as a cancer chemotherapeutic agent. Utilizing a 125I-labeled bisamino-modified derivative, the distribution, excretion, and metabolism of NCS have been studied in normal and tumor-bearing rodents.

NCS is rapidly excreted in the urine, with about 55% of the drug excreted unchanged in the first hr. About 10% of the radioactivity remained in the blood 1 hr after administration and was associated with peptides with molecular weights of ∼1500; these were not detected in the urine. The mean urinary excretion half-life of 1.65 hr was less than the apparent elimination half-life from blood (6.2 hr). Biliary excretion contributed little to the total clearance of NCS, since only a small fraction of the drug appeared unchanged in the bile. Although biliary excretion increased in the anephric rat, it proceeded at a maximum rate of 0.25 to 0.3%/hr. Tissue levels of 125I-NCS were highest in kidney, the principal organ of excretion. Decreasing levels were observed in the skin, lung, intestine, pancreas, liver, spleen, muscle, thymus, and bone. 125I-NCS was low in the testis and practically excluded from the brain. Radioactivity due to 125I-NCS persisted in the Walker 256 ascites tumor in the rat but not in the ascites of the L1210 leukemia in mice. Since there is rapid elimination of the drug from the central compartment and little persistence in the tissues 6 hr after single (i.v.) injection, optimal scheduling may be frequent single injections or short continuous-flow infusions.

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This investigation was supported by National Cancer Institute Research Grants CA 17305 and CA 06516.

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