Synthesis, in vivo rhesus monkey biodistribution and in vitro evaluation of a 11C-labelled potent aromatase inhibitor:: [N-methyl-11C]vorozole
Synthesis, in vivo rhesus monkey biodistribution and in vitro evaluation of a 11C-labelled potent aromatase inhibitor:: [N-methyl-11C]vorozole
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DOI：
10.1016/s0969-8051(98)00009-2
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发表时间：
1998-07-01
影响因子：
3.1
通讯作者：
Langstrom, B
中科院分区：
文献类型：
--
作者：
Lidstrom, P;Bonasera, TA;Langstrom, B
[N-甲基-C-11]沃洛唑是一种高亲和力的芳香酶结合放射性示踪剂，通过[C-11]甲基碘对其进行N-甲基化反应合成。在放射性核素生产结束后的40分钟内，以[C-11]甲基碘为基准，以53-56%的放化产率得到了[N-甲基-C-11]沃洛唑。最终处方的放化纯度为98%，比放射性为10-143GBq/mMol。在体外，[N-甲基-C-11]沃洛唑与富含芳香酶的人胎盘显示出高度的特异性结合。[N-甲基-C-11]沃洛唑与其他组织的结合力较低，特异性较差。测得的离解常数在较低的NHL范围内(K(D)1.7 nm)，与已发表的Vorozole的K-I值一致。在恒河猴体内的生物分布研究表明，恒定的肝脏摄取率在10分钟后达到注射剂量的20%，除此之外，放射性分布相对均匀。用沃拉唑预处理仅对示踪剂的生物分布造成轻微的改变。《核医学生物》25；5：497-501,1998。(C)1998年爱思唯尔科学公司。
[N-methyl-C-11]Vorozole, a high-affinity aromatase-binding radiotracer, was synthesized through N-methylation of the corresponding nor-vorozole derivative using [C-11]methyl iodide. [N-methyl-C-11]Vorozole was obtained in 53-56% radiochemical yield based on [C-11]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/mu mol. In vitro, [N-methyl-C-11]vorozole displayed high and specific binding to aromatase rich human placenta. [N-methyl-C-11]Vorozole binding to other tissues was lower and less specific. The dissociation constant measured was in the low nhl range (K(d )1.7 nM), consistent with published K-i 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. NUCL MED BIOL 25;5:497-501, 1998. (C) 1998 Elsevier Science Inc.