The blood-brain transfer, protein incorporation and metabolism of L-[75Se]selenomethionine (SeMet) of relatively high specific activity (> 400 GBq mmol) were studied in male Wistar rats. The highest uptake was found in the pancreas, followed by the tumor, kidney, liver, brain and muscle. In addition, plasma and brain samples of rats were analyzed for labeled fractions of free SeMet, metabolites, and SeMet bound to t-RNA and proteins. For example, free SeMet represented more than 80% of brain radioactivity at 1.5 min while it was less than 15% at 360 min. A concomitant increase was observed for protein bound SeMet in brain. A three-compartment model was applied to calculate the blood-brain transfer constant (K1 (0.15 +/- 0.070 mL g-1 min-1) and the rate constant of SeMet incorporation into proteins (k3 = 0.026 +/- 0.008 min-1). The apparent incorporation of methionine into proteins was estimated to be about 0.73 nmol g-1 min-1. From the studies it is concluded that the use of L-[75Se]selenomethionine may be appropriate to measure brain protein incorporation in humans with PET.