The in vivo behavior of 20-[18F]fluoroarachidonic acid (18F-FAA) was investigated to evaluate its potential use as a radiotracer for studying the regional brain and heart lipid metabolism by positron emission tomography (PET). Tissue biodistribution studies in rats have revealed that 18F-FAA has a high uptake in the liver and lung, thus probably reflecting the metabolism, and is accompanied by both low in vivo defluorination and low blood levels. At 30 min postinjection, the uptake in the brain and heart reached values of 0.26 +/- 0.02 and 1.22 +/- 0.58% dose/g, respectively, with ratios to the blood radioactivity of 1.04 and 4.88, respectively. Lipid extraction at 30 min postinjection showed that 39% of the brain radioactivity was in the organic phase whereas the organic phase from heart tissue contained 73% of the total radioactivity. A TLC analysis demonstrated that 18F-FAA was mainly bound to phospholipids in the brain and heart tissue as expected. Based on the findings of this study, the utility of 18F-FAA as an in vivo tracer for cerebral phospholipid studies appears to be limited because of its relatively high radioactivity in the aqueous brain fraction. However, our findings do suggest that this agent might be useful as a tool for studies of cardiac phospholipid turnover, even though it demonstrated a poor heart-to-lung and heart-to-liver contrast.