Jack D. Davidson

The physiological disposition of the carcinostatic 1,3‐bis(2‐chloroethyU‐l‐nitrosourea (BCNU) in man and animals

The pharmacology of BCNU, an active antitumor agent in animal and man, was studied with the use of the C14‐labeled drug. Radioactivity was excreted slowly in man and monkeys and rapidly in mice. Urinary excretion accounted for the maior portion of the isotope although as much as ten per cent was excreted as CO,. The compound is rapidly degraded and promptly after administration no intact drug is demonstrable, although plasma levels of the isotope are prolonged by protein binding of a portion of the drug. Part of the drug may be recirculated in the bile and partially accounts for the prolonged plasma levels. The drug is stable in an acid milieu and well absorbed orally. Its high lipid solubility allows it to readily cross the blood‐brain barrier. The active moiety of this agent is still unknown. The contrast of the short biologic half‐life of intact BCNU to the delayed clinical toxicity and prolonged plasma levels of carbon‐14 is interesting.

Tritium and Carbon-14 by Oxygen Flask Combustion

In the fall of 1961, with the help of Donald Buyske, then of Lederle Laboratories, our group in chemical pharmacology at the National Cancer Institute set up the technique for the oxygen flask combustion of biological samples for the determination of radiocarbon and tritium [1, 2]. After a few months’ experience we introduced a number of modifications in the technique from that originally described by Kelly et al. of the Lederle group, and we published the substance of these as a short communication the following summer [3]. During the next 4 years we continued to use this technique and have directly helped about a dozen other groups get started with this method. During these intervening years, a host of publications have appeared, detailing variations on the equipment and technique. Some offer advantages over our technique for certain purposes, but most have impressed us as involving unnecessary complication, expense, or even hazard. The purpose of this presentation is to provide a cookbook version of our entire technique that hopefully will be complete within itself and will make this simplified method of handling biological samples conveniently available to the numbers of people that we think could profitably use it.