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Cancer Chemother Pharmacol. 1982 Dec;10(1):16-21.

Distribution of 13N in rat tissues following intravenous administration of nitroso-labeled BCNU.


The concentrations of label in 16 major organs and tissues of pentobarbital-sedated normal male rats were measured at six time points ranging from 0.2 to 50 min after IV injection of the antitumor drug BCNU labeled in the nitroso position with cyclotron-produced nitrogen-13. Initial (12-s) concentrations in the lungs, kidneys, and heart were 41, 13, and 11 times the whole-body average, respectively. Time for clearance of the first 50% of the injected dose from the circulation was of the order of several seconds. Estimated first-pass extractions of 70% or more were noted in the heart, kidneys, brain, stomach, small intestine, muscle, fat, and bone. Washout of label from the heart and lungs was quite rapid, removing most of the initially extracted 13N from these organs by 2 min after injection. Label concentrations in the kidneys exceeded those in all other tissues studied between 2 and 50 min. Secondary accumulations of 13N were observed in muscle, skin, liver, small intestine, and fat. Label concentrations in a number of tissues closely paralleled the steadily decreasing concentration in blood for various intervals between 5 and 50 min. The results suggest that the toxic insult to lung tissue from IV administered BCNU is effected in a period of several minutes. They also suggest that intra-arterial administration of the drug would significantly raise the target/non-target dose ratio and lower the incidence of pulmonary toxicity.

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