Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia: A PET study in rat and canine models of focal cerebral ischemia

Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the TCA cycle after beta-oxidation. We speculate that 1-11C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of 1-11C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of 15O]H2O measured 1-2 h and 5-6 h after insult was compared with that of 1-11C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with 15O]H2O were lower than those determined with 1-11C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of 1-11C]octanoate was observed in the ischemic regions. The uptake of 1-11C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that 1-11C]octanoate provides functional information different from CBF. In conclusion, we found that 1-11C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia.