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 [1-11C]hexanoate has a biphasic pattern, the second phase being determined by peripherally originating [11C]CO2/HCO3-, and therefore does not reflect the metabolism of 11C-labeled fatty acid in the brain.