Positron emission tomography (PET) was performed on the cat brain to characterize [1-11C]hexanoate and other [1-11C]labeled short and medium-chain fatty acids as a tracer of fatty acid oxidative metabolism. After an intravenous injection the brain uptake of [1-11C]hexanoate reached a peak followed by rapid washout until 2 min (first phase). Subsequently the total brain uptake was again increased and reached to a peak 7–10 min after tracer injection (second phase). The blood radioactivity of unmetabolized [1-11C]hexanoate was rapidly decreased and almost eliminated within the first 2 min, whereas the blood radioactivity of [11C]CO2/HCO3− was gradually increased and reached a peak approximately 5 min after tracer injection. As the effect of circulating [11C]CO2/ HCO3− was examined by a bolus intravenous injection of [11C]CO2/HCO3−, the brain uptake of [11C]CO2/HCO3− was rapidly increased right after the injection and changed parallel to the blood level of [11C]CO2/HCO3−.
These results suggest that, in contrast to the previous mouse data, the time-activity curve in the cat brain following intravenous injection of [l-11C]hexanoate has a biphasic pattern, the second phase being determined by peripherally originating [11C]CO2/HCO3−, and therefore does not reflect the metabolism of11C-labeled fatty acid in the brain.
hexanoate fatty acid brain cats PET
This is a preview of subscription content, log in to check access
Hawkins RA, Mans AM, Davis DW, Vina JR, Hibbard LS. Cerebral glucose use measured with [14C]glucose labeled in the 1, 2, or 6 position.Am J Physiol 248: C170-C176, 1985.PubMedGoogle Scholar
Cremer JE, Teal HM, Heath DF, Cavanagh JB. The influence of portocaval anastomosis on the metabolism of labeled octanoate, butyrate and leucine in rat brain.J Neurochem 28: 215–222, 1974.CrossRefGoogle Scholar
Rowley H, Collins RC. [1-14C]octanoate: a fast functional marker of brain activity.Brain Res 335: 326–329, 1985.PubMedCrossRefGoogle Scholar
Ishiwata K, Ishii K, Ogawa K, Nozaki T, Senda M. A brain uptake study of [l-11C]hexanoate in the mouse: the effect of hypoxia, starvation and substrate competition.Ann Nucl Med 10: 265–270, 1996.PubMedCrossRefGoogle Scholar
Oldendorf WH. Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids.Am J Physiol 224: 1450–1453, 1973.PubMedGoogle Scholar
Ishiwata K, Ishii K, Ogawa K, Sasaki T, Toyama H, Ishii S, et al. Synthesis and preliminary evaluation of [1-11C]hexanoate as a PET tracer of fatty acid metabolism.Ann Nucl Med 9: 51–57, 1995.PubMedGoogle Scholar
Watanabe M, Uchida H, Okada K, Shimizu K, Satoh E, Yoshikawa T, et al. A high resolution PET for animal studies.IEEE Trans Med Imag 11: 577–580, 1992.CrossRefGoogle Scholar
Shields AF, Graham MM, Kozawa SM, Kozell LB, Link JM, Swenson ER, et al. Contribution of labeled carbon dioxide to PET imaging of carbon-11-labeled compounds.J Nucl Med 33: 581–586, 1992.PubMedGoogle Scholar
Kuge Y, Yajima K, Kawashima H, Yamazaki H, Hashimoto N, Miyake Y. Brain uptake and metabolism of [l-11C]octanoate in rats: Pharmacokinetic basis for its application as a radiopharmaceutical for studying brain fatty acid metabolism.Ann Nucl Med 9: 137–142, 1995.PubMedGoogle Scholar