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

Journal Article · · J. Pharmacol. Exp. Ther.; (United States)
OSTI ID:7230367
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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 (C/sub 4/--C/sub 10/ and C/sub 13/) labeled with carbon-11 (T/sub 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 C/sub 4/ through C/sub 10/ 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 (-NH/sub 2/, -C identical with N, -CO/sub 2/H, -OH) showed that the amino group as well as the relatively lipophilic alkyl group were required for lung specificity. The /sup 11/C-aliphatic amines were rapidly metabolized via monoamine oxidase (ultimately to /sup 11/CO/sub 2/). 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 /sup 11/CO/sub 2/ excretion, and iproniazid significantly increased the radioactivity retained by the brain, lungs and liver at 15 minutes. The rate of /sup 11/CO/sub 2/ excretion depended on carbon chain length (C/sub 4/ < C/sub 5/< C/sub 6/ > C/sub 7/ > C/sub 8/ > C/sub 9/ > C/sub 10/ > C/sub 13/).

Research Organization:
Brookhaven National Lab., Upton, NY
OSTI ID:
7230367
Journal Information:
J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 198:1; ISSN JPETA
Country of Publication:
United States
Language:
English

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Related Subjects

560172* -- Radiation Effects-- Nuclide Kinetics &amp; Toxicology-- Animals-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
BOND LENGTHS
CARBON 11
CARBON COMPOUNDS
CARBON DIOXIDE
CARBON ISOTOPES
CARBON OXIDES
CHALCOGENIDES
CLEARANCE
EVEN-ODD NUCLEI
EXCRETION
ISOTOPES
LABELLING
LIGHT NUCLEI
LUNGS
MAMMALS
METABOLISM
MICE
MINUTES LIVING RADIOISOTOPES
NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
RADIOISOTOPES
RADIONUCLIDE KINETICS
RESPIRATORY SYSTEM
RODENTS
TISSUES
UPTAKE
VERTEBRATES