ポジトロン断層法によるヒト脳ドーパミン代謝測定へのF-18標識プロドラッグの応用

在体内评价了氟化多巴前药作为PET研究突触前多巴胺代谢的示踪剂的潜力。6-[^<18>F]氟- o- pivalyl - l- dopa （6-[^<18>F]FPDOPA）是由4- o- pivalyl - l- dopa与乙酰[^<18>F]次萤石直接氟化制备的。小鼠对该化合物的脑摄取低于6-[^<18>F]FDOPA；然而，6-[^<18>F]fdopa中纹状体对其他参考区域的吸收比大于6-[^<18>F]fdopa。芳香氨基酸脱羧酶和儿茶酚- o -甲基转移酶抑制剂增强纹状体的选择性摄取；6-[^<18>F]FDOPA的效果小于6-[^<18>F]FDOPA。l -苯丙氨酸负载降低了这两种化合物的脑摄取，这表明化合物通过血脑屏障的运输是由中性氨基酸转运系统介导的。HPLC分析发现纹状体中存在6-[^<18>F]FPDOPA、6-[^<18>F]FDOPA、6-[^<18>F]氟多巴胺等代谢物，但其他脑区未发现6-[^<18>F]氟多巴胺。结果表明，6-[^<18>F]FPDOPA具有作为多巴前药的潜力。6-[^<18>F]FDOPA经盐酸水解后，用缓冲生理盐水作为洗脱液进行高效液相色谱分离，得到无菌无孕6-[^<18>F]FDOPA注射液。与以前报道的方法相比，该方法适用于人体PET研究的常规生产。在使用6-[^<18>F]FDOPA的人体PET研究中，通过PET获得的大脑代谢图像与MRI获得的结构图像精确地叠加，已经发展起来。在正常受试者中进行了纹状体域胺代谢的半定量评估。

The potential of a fluorinated dopa prodrug as a tracer for studying presynaptic dopamine metabolism by PET was evaluaed in vivo. 6-[^<18>F]fluoro-O-pivaloyl-L-dopa (6-[^<18>F]FPDOPA) was prepared by direct fluorination of 4-O-pIVALOYl-L-dopa with acetyl [^<18>F]hypofluorite. In mice, brain uptake of the compound was lower than that of 6-[^<18>F]FDOPA ; however, the uptake ratios of striatum-to-other reference regions was larger in the 6-[^<18>F]FPDOPA than in the 6-[^<18>F]fdopa. Inhibitors of aromatic amino acid decarboxylase and catechol-O-methyl transferase enhanced selective uptake by the striatum ; the effect was smaller for 6-[^<18>F]FPDOPA than for 6-[^<18>F]FDOPA.reduced brain uptake of both compounds by L-phenylalanine-loading suggested that transport of the compounds across the blood-brain barrier was mediated by the neutral amino acid transoport system. BY HPLC analysis, 6-[^<18>F]FPDOPA, 6-[^<18>F]FDOPA, 6-[^<18>F]fluorodopamine and other metabolies were found in the striatum, although 6-[^<18>F]fluorodopamine was not found in other brain regions. The results show the potential of 6-[^<18>F]FPDOPA as a dopa prodrug.The HCl-hydrysis of 6-[^<18>F]FPDOPA followed by HPLC separation using the buffered physiological saline as an eluting solution, gave a steril and apyrogenic 6-[^<18>F]FDOPA injection. The method was suitable for routine production in human PET studies as compared to the methods reported prevously. In human PET studies using 6-[^<18>F]FDOPA, the metabolic images of the brain obtained by PET were superimposed precicely to the structual images obatined by MRI, has been developed. Semi-quantitative assesment of doamine metabolism in the striatum has been performed in normal subjects.