PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada M5T 1R8.
Nucl Med Biol. 2011 Oct;38(7):933-43. doi: 10.1016/j.nucmedbio.2011.03.003. Epub 2011 Jun 17.
Imaging monoamine oxidase B (MAO-B) in the central nervous system with PET is an important goal for psychiatric studies. We here report an improved and automated radiosynthesis of N-(6-[(18)F]-fluorohexyl)-N-methylpropargylamine ([(18)F]FHMP; [(18)F]-1), as well as the radiosynthesis of two new promising candidates for imaging cerebral MAO-B, namely, carbon-11-labeled 3-(4-[(11)C]-methoxyphenyl)-6-methyl-2H-1-benzopyran-2-one ([(11)C]-2) and N-((1H-pyrrol-2-yl)methyl)-N-[(11)C]-methyl-1-phenylmethanamine ([(11)C]-3).
Fluorine-18-labeled 1 was prepared via a tosyloxy precursor in 29%±5% uncorrected radiochemical yield, relative to [(18)F]-fluoride. Both carbon-11-labeled compounds were prepared with [(11)C]CH(3)I using the "LOOP" method in 11% and 18% uncorrected radiochemical yields, respectively, relative to starting [(11)C]CO(2). All radiotracers had specific activities >37 GBq/μmol and were >98% radiochemically pure at end of synthesis (<40 min). All radiotracers were evaluated by ex vivo biodistribution studies in conscious rodents.
A major radioactive metabolite in the rodent brain was observed following administration of [(18)F]-1. While [(11)C]-2 had moderate brain penetration and good clearance from normal brain tissue, distribution of radioactivity in brain was indicative of free and nonspecific binding. Good brain uptake was observed with [(11)C]-3 (0.8%-1.4% injected dose per gram at 5 min postinjection), binding appeared to be reversible and distribution conformed with regional distribution of MAO-B in the rat brain. Preinjection of 3 or L-deprenyl showed a modest reduction (up to 25%) of brain activity.
Carbon-11-labeled 3 was found to have the most favorable properties of the radiotracers evaluated; however, the signal-to-noise ratio was too low to warrant further in vivo imaging studies. Alternative radiotracers for imaging MAO-B are under development.
使用正电子发射断层扫描（PET）对中枢神经系统中单胺氧化酶 B（MAO-B）进行成像，是精神科研究的一个重要目标。我们在此报告一种改进和自动化的放射性合成 N-（6-[[18]F]-氟己基]-N-甲基炔丙胺（[（18）F]FHMP；[（18）F]-1）的方法，以及两种用于成像脑 MAO-B 的新型有前途的候选放射性示踪剂，即碳-11 标记的 3-（4-[[11]C]-甲氧基苯基）-6-甲基-2H-1-苯并吡喃-2-酮（[（11）C]-2）和 N-（（1H-吡咯-2-基）甲基）-N-[[11]C]-甲基-1-苯甲胺（[（11）C]-3）的放射性合成。
通过甲苯磺酰氧基前体以 29%±5%未经校正的放射化学产率（相对于[（18）F]-氟化物）制备氟-18 标记的 1。使用“LOOP”方法，分别以 11%和 18%未经校正的放射化学产率（相对于起始[（11）C]CO2），用[（11）C]CH3I 制备了两种碳-11 标记的化合物。所有放射性示踪剂的比活度均>37GBq/μmol，在合成结束时（<40min）>98%为放射化学纯。所有放射性示踪剂均通过清醒啮齿动物的体外生物分布研究进行评估。
在给予[（18）F]-1 后，在啮齿动物脑中观察到主要的放射性代谢产物。虽然[（11）C]-2 具有中等的脑穿透性，且可从正常脑组织中快速清除，但放射性在脑中的分布表明存在游离和非特异性结合。[（11）C]-3 具有良好的脑摄取（注射后 5min 时为 0.8%-1.4%注射剂量/克），结合似乎是可逆的，且分布与大鼠脑 MAO-B 的区域分布一致。预先注射 3 或 L-deprenyl 可使脑活性适度降低（最多 25%）。
评估的放射性示踪剂中，[（11）C]-3 具有最有利的特性；然而，由于信号与噪声比太低，因此不支持进一步进行体内成像研究。正在开发用于 MAO-B 成像的替代放射性示踪剂。
