Carbon-11 labeled aliphatic amines in lung uptake and metabolism studies: potential for dynamic measurements in vivo

JS Fowler, BM Gallagher, RR MacGregor and AP Wolf

In order to assess the potential utility of amines labeled with short- lived nuclides as agents for lung imaging and function studies in humans, a series of aliphatic amines (C4-C10 and C13) labeled with carbon-11 (T 1/2 = 20.4 minutes), which decays by the emission of body- penetrating radiation, has been used as a model for studying some basic parameters affecting amine uptake and metabolism by the lung and other tissues in mice. The lung uptake (percentage of dose per organ) of aliphatic amines at 1 minute increased from 2.18 +/- 0.13% for butylamine to 13.33 +/- 0.84% for tridecylamine. Partition coefficients (between n-octanol and pH = 7 buffer) were measured for the C4 through C10 amines and for octanoic acid and octanenitrile. Within the amine series, the partition coefficient correlated with lung uptake. A comparison of a series of compounds all having a carbon chain length of eight but with different functional groups (--NH2, --C=N, --CO2H, --OH) showed that the amino group as well as the relatively lipophilic alkyl group were required for lung specificity. The 11C-aliphatic amines were rapidly metabolized via monoamine oxidase (ultimately to 11CO2). Non- amine metabolites in blood and lungs at 5 minutes postinjection were 95 and 50%, respectively. Pretreatment of mice with iproniazid and with pargyline decreased 11CO2 excretion, and iproniazid significantly increased the radioactivity retained by the brain, lungs and liver at 15 minutes. The rate of 11CO2 excretion depended on carbon chain length (C4 less than C5 less than C6 greater than C7 greater than C8 greater than C9 greater than C10 greater than C13).

Volume 198, Issue 1, pp. 133-145, 07/01/1976
Copyright © 1976 by American Society for Pharmacology and Experimental Therapeutics