Evaluation of [¹⁴C]phenylacetate as a prototype tracer for the measurement of glial metabolism in the rat brain

Abstract 

[¹⁴C]Phenylacetate was designed as a prototype tracer for the measurement of glial metabolism, and its potency in comparison with that of [¹⁴C]acetate was evaluated in this study. Normal rats were intravenously injected with [¹⁴C]phenylacetate or [¹⁴C]acetate, and radioactivity concentrations were measured in the plasma, cerebral cortex, cerebellum and peripheral tissues by dissection method. In addition, [¹⁴C]phenylacetate uptake in the rat brain was compared by autoradiography with that of [¹⁴C]acetate following the injection of fluorocitrate, a selective glial toxin, into the brain. [¹⁴C]Phenylacetate was rapidly taken up into the brain and was retained at high levels up to 20 min postadministration. The levels of [¹⁴C]phenylacetate in the cerebral cortex were about threefold higher than those of [¹⁴C]acetate at 1 min postinjection. Microinjection of fluorocitrate into the right striatum resulted in a significant decrease of the uptake of both [¹⁴C]phenylacetate and [¹⁴C]acetate into the right striatum. Radiochemical analysis confirmed the rapid hydrolysis of [¹⁴C]phenylacetate in the rat brain, with less than 20% of radioactivity representing unmetabolized [¹⁴C]phenylacetate at 1 min postinjection. These results suggest that [¹⁴C]phenylacetate is rapidly taken up into the brain and is hydrolyzed and converted to [¹⁴C]acetate. [¹⁴C]Phenylacetate may have the potential to serve as a tracer for the measurement of glial metabolism in an intact brain.

Keywords: [¹⁴C]Phenylacetate, Hydrolysis, Carboxylesterase, Rat, Brain