[¹⁴C]Benzyl acetate is a potential radiotracer for the measurement of glial metabolism in the rat brain

Abstract 

In order to develop a suitable radiotracer for the measurement of glial metabolism, we synthesized four different types of ester derivatives of [¹⁴C]acetate, namely, [¹⁴C]phenyl acetate, [¹⁴C]para-nitrophenyl acetate, [¹⁴C]2,4-dinitrophenyl acetate and [¹⁴C]benzyl acetate ([¹⁴C]BA), and evaluated their potencies in rats. Among the derivatives, the highest brain uptake at 30 s postinjection was observed for [¹⁴C]BA, which was more than 23 times higher than that of [¹⁴C]acetate itself. A long-term retention of [¹⁴C]BA radioactivity in the brain was observed, whereas rapid clearance of radioactivity was seen in the heart. [¹⁴C]BA was rapidly hydrolyzed in the intact rat brain, and less than 5% of radiolabeled parent was observed 1 min after the injection. Radiochemical analysis using thin-layer chromatography revealed that [¹⁴C]BA was rapidly converted to [¹⁴C]glutamine and [¹⁴C]glutamate in the cortex within 10 min after injection. Furthermore, the uptake of [¹⁴C]BA was significantly decreased following microinjection of fluorocitrate, a selective glial toxin. These results strongly suggest that [¹⁴C]BA may be a useful radiotracer for the measurement of glial metabolism in the intact rat brain.

Keywords: Phenyl acetate derivatives, Benzyl acetate, Glial metabolism, Brain, In vivo