Validation of a tracer kinetic model for the quantification of 5-HT2A receptors in human brain with [11C]MDL 100,907
Validation of a tracer kinetic model for the quantification of 5-HT2A receptors in human brain with [11C]MDL 100,907
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DOI：
10.1038/sj.jcbfm.9600323
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发表时间：
2007-01-01
影响因子：
6.3
通讯作者：
Grasby, Paul M.
中科院分区：
文献类型：
--
作者：
Hinz, Rainer;Bhagwagar, Zubin;Grasby, Paul M.
正电子发射断层扫描（PET）配体[C-11] MDL 100，907先前已被引入对人脑中的5-羟色胺2A（5-HT 2A）受体进行成像。这项工作的目的是有助于在人体研究中的示踪动力学建模的验证。在静脉推注约370 MBq [C-11] MDL 100，907后，使用动态PET对5名健康志愿者进行两次扫描。一次扫描在基线条件下进行，另一次扫描在单次口服30 mg抗抑郁药米氮平（与5-HT 2A受体结合）后90分钟开始。人血浆中似乎不存在可能穿过血脑屏障的[C-11] MDL 100，907放射性标记代谢物。使用可逆、两个组织、四个速率常数房室模型（具有可变分数血容量项和代谢物校正血浆输入函数）估计11个不同脑区的总分布容积VD。在基线和阻断扫描之间，小脑中的VD没有显著变化，证实小脑是一个没有可置换结合的区域。然后使用计算的小脑VD和occupancy间接获得结合潜力的区域估计。该临床有效剂量米氮平的平均使用率为60%，无显著地区差异。本研究证实了使用动脉输入动力学模型定量5-HT 2A受体与[C-11] MDL 100，907的结合，并使用小脑作为游离和非特异性结合的参考区域。
The positron emission tomography ( PET) ligand [C-11] MDL 100,907 has previously been introduced to image the serotonin 2A (5-HT2A) receptor in human brain. The aim of this work was to contribute to the verification of the tracer kinetic modelling in human studies. Five healthy volunteers were scanned twice after intravenous bolus injection of approximately 370MBq [C-11] MDL 100,907 using dynamic PET. One scan was performed under baseline condition, the other scan commenced 90 mins after a single oral dose of 30mg of the antidepressant mirtazapine, which binds to the 5-HT2A receptor. There did not appear to be radiolabelled metabolites of [C-11] MDL 100,907 in human plasma, which are likely to cross the blood - brain barrier. Total volumes of distribution VD in 11 different brain regions were estimated using a reversible, two tissue, four rate constants compartment model with a variable fractional blood volume term and the metabolite- corrected plasma input function. There were no significant changes of the VD in the cerebellum between the baseline and the blocked scans confirming the cerebellum as a region devoid of displaceable binding. Regional estimates of binding potential were then obtained indirectly using the cerebellar VD and occupancies calculated. The mean occupancy with this clinically effective dose of mirtazapine was 60% without significant regional differences. This study confirmed the use of an arterial input kinetic model for the quantification of 5- HT2A receptor binding with [C-11] MDL 100,907 and the use of the cerebellum as a reference region for the free and nonspecific binding.