Momosaki Sotaro, Hosoi Rie, Sanuki Tomoya, Todoroki Kenichiro, Yamaguchi Masatoshi, Gee Antony, Inoue Osamu
Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Nucl Med Biol. 2007 Nov;34(8):939-44. doi: 10.1016/j.nucmedbio.2007.06.011. Epub 2007 Sep 4.
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.
为了开发一种适用于测量神经胶质细胞代谢的放射性示踪剂，我们合成了四种不同类型的[14C]乙酸酯衍生物，即[14C]苯乙酸酯、[14C]对硝基苯乙酸酯、[14C]2,4-二硝基苯乙酸酯和[14C]苄基乙酸酯（[14C]BA），并在大鼠中评估了它们的效能。在这些衍生物中，注射后30秒时[14C]BA在脑中的摄取量最高，比[14C]乙酸本身高出23倍以上。观察到[14C]BA放射性在脑中的长期滞留，而在心脏中则观察到放射性的快速清除。[14C]BA在完整的大鼠脑中迅速水解，注射后1分钟时观察到放射性标记的母体不到5%。使用薄层色谱法进行的放射化学分析表明，注射后10分钟内[14C]BA在皮质中迅速转化为[14C]谷氨酰胺和[14C]谷氨酸。此外，在显微注射选择性神经胶质毒素氟代柠檬酸后，[14C]BA的摄取量显著降低。这些结果强烈表明，[14C]BA可能是一种用于测量完整大鼠脑中神经胶质细胞代谢的有用放射性示踪剂。
