Bormans G, Sherman P, Snyder S E, Kilbourn M R
Laboratory for Radiopharmaceutical Chemistry, K.U. Leuven, Belgium.
Nucl Med Biol. 1996 May;23(4):513-7. doi: 10.1016/0969-8051(96)00033-9.
Carbon-11- and fluorine-18-labeled forms of 1-methyl-4-piperidyl-4'-fluorobenzoate were prepared as potential in vivo substrates for brain acetylcholinesterase. The 1-methyl-4-piperidyl-4'-[18F]fluorobenzoate was prepared by aromatic nucleophilic substitution using the nitro precursor and no-carrier added [18F]fluoride ion. The 1-[11C]methyl-4-piperidyl-4'-fluorobenzoate was synthesized by N-[11C]methylation of the appropriate nor-methyl precursor. Biodistribution studies in mice showed high brain uptake of these radiotracers followed by a fast washout with no significant retention of radioactivity in areas of high acetylcholinesterase enzymatic activity. This is contrasted with 1-[11C]methyl-4-piperidylacetate, which is rapidly trapped in brain tissues through hydrolysis by AChE. Further in vivo and in vitro studies demonstrated that 1-methyl-4-piperidyl-4'-fluorobenzoate was not a substrate for AChE, and thus not suitable as an in vivo radiotracer for studying this enzyme in the brain.
制备了碳-11和氟-18标记的1-甲基-4-哌啶基-4'-氟苯甲酸酯，作为脑乙酰胆碱酯酶潜在的体内底物。1-甲基-4-哌啶基-4'-[18F]氟苯甲酸酯通过使用硝基前体和无载体添加的[18F]氟离子进行芳环亲核取代反应制备。1-[11C]甲基-4-哌啶基-4'-氟苯甲酸酯通过适当的去甲基前体的N-[11C]甲基化反应合成。小鼠体内分布研究表明，这些放射性示踪剂在脑中摄取较高，随后快速清除，在高乙酰胆碱酯酶活性区域无明显放射性滞留。这与1-[11C]甲基-4-哌啶基乙酸酯形成对比，后者通过乙酰胆碱酯酶水解迅速被困在脑组织中。进一步的体内和体外研究表明，1-甲基-4-哌啶基-4'-氟苯甲酸酯不是乙酰胆碱酯酶的底物，因此不适合作为体内放射性示踪剂用于研究脑中的该酶。
