CARBON-11 LABELED ALIPHATIC-AMINES IN LUNG UPTAKE AND METABOLISM STUDIES - POTENTIAL FOR DYNAMIC MEASUREMENTS INVIVO

Abstract

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 11 C 11 (T1/2 = 20.4 min), which decays by the emission of body-penetrating radiation, [half life] was used as a model in the mouse 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 min 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 C chain length of 8 but with different functional groups (.sbd.NH2,.sbd.C.tbd.N,.sbd.CO2H,.sbd.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 min 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 brains, lungs and liver at 15 min. The rate of 11CO2 excretion depended on C chain length (C4 < C5 < C6 > C7 > C8 > C9 > C10 > C13).