Lidström P, Bonasera T A, Kirilovas D, Lindblom B, Lu L, Bergström E, Bergström M, Westlin J E, Långström B
Department of Organic Chemistry, Uppsala University, Sweden.
Nucl Med Biol. 1998 Jul;25(5):497-501. doi: 10.1016/s0969-8051(98)00009-2.
[N-methyl-11C]Vorozole, a high-affinity aromatase-binding radiotracer, was synthesized through N-methylation of the corresponding nor-vorozole derivative using [11C]methyl iodide. [N-methyl-11C]Vorozole was obtained in 53-56% radiochemical yield based on [11C]methyl iodide within 40 min of the end of radionuclide production. The final formulation was >98% radiochemically pure and had a specific radioactivity of 10-143 GBq/micromol. In vitro, [N-methyl-11C]vorozole displayed high and specific binding to aromatase-rich human placenta. [N-methyl-11C]Vorozole binding to other tissues was lower and less specific. The dissociation constant measured was in the low nM range (Kd 1.7 nM), consistent with published Ki values for vorozole. Biodistribution studies in rhesus monkeys showed high liver uptake, which reached a constant level of 20% of the injected dose after 10 min, and an otherwise relatively even distribution of radioactivity. Pretreatment with vorozole only caused minor alterations of the biodistribution of the tracer.
[甲基 - 11C]伏洛唑是一种高亲和力的芳香化酶结合放射性示踪剂，通过使用[11C]碘甲烷对相应的去甲基伏洛唑衍生物进行N - 甲基化反应合成。基于放射性核素生产结束后40分钟内的[11C]碘甲烷，[甲基 - 11C]伏洛唑的放射化学产率为53 - 56%。最终制剂的放射化学纯度>98%，比活度为10 - 143 GBq/微摩尔。在体外，[甲基 - 11C]伏洛唑对富含芳香化酶的人胎盘显示出高特异性结合。[甲基 - 11C]伏洛唑与其他组织的结合较低且特异性较差。测得的解离常数在低纳摩尔范围内（Kd 1.7纳摩尔），与已发表的伏洛唑Ki值一致。恒河猴的生物分布研究显示肝脏摄取较高，10分钟后达到注射剂量的20%的恒定水平，放射性在其他方面分布相对均匀。用伏洛唑预处理仅引起示踪剂生物分布的轻微改变。
