PET imaging of monoamine oxidase B in peripheral organs in humans.-猫眼课题宝

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发表时间：

2002-10

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Journal of nuclear medicine : official publication, Society of Nuclear Medicine

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其他

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作者：

J. Fowler;J. Logan;Gene-Jack Wang;N. Volkow;Wei Zhu;D. Franceschi;N. Pappas;R. Ferrieri;C. Shea;V. Garza;Youwen Xu;R. Macgregor;D. Schlyer;S. Gatley;Yu-Shin Ding;D. Alexoff

未标记单胺氧化酶(MAO)调节脑内神经递质浓度，也是外周器官的重要解毒酶。它出现在两个亚型，MAO A和MAO B。它们在不同器官中的相对比例因特定的器官和物种而异，因此很难推断从动物到人类的衡量标准。本研究的目的是探讨用正电子发射计算机断层扫描(PET)对人体外周器官进行MAO-B显像的可行性。方法对9例健康受试者(男7例，女2例；平均年龄+/-SD，37+/-7岁)分别用~(11)C-L-去戊烯和~(11)C-L去甲肾上腺素(~(11)C-L-去戊烯-D2)进行2次躯干区动态正电子发射计算机断层扫描。每项研究都测量了心、肺、肝、肾和脾的时间-活动曲线和动脉血浆输入。比较平台期摄取和掺入商(IQ=摄取/血浆输入)以及模型项K1(它是血流量的函数)和K3和lambdak3(与MAO B成正比的动力学项)，以识别那些显示MAO B的重离子替代(氚同位素效应)特征的减值器官。此外，敏感性分析比较了两种示踪剂定量MAO B的能力。结果心、肺、肾和脾对MAO B的摄取、IQ、K3和Lambdak3有很强的氘同位素效应。~(11)C-L-丙戊烯-D2的动脉血浆输入功能显著大于~(11)C-L-丙戊烯。肝脏的时间-活度曲线不受氚替代的影响，也不能估计模型项。在表现出同位素效应的器官中，lambdak3的排列顺序为：肾和GT；或=心和GT；肺=脾。敏感性分析表明，~(11)C-L-丙烯基-D2比~(11)C-L-丙烯基更能反映MAO活性。结论本研究表明：(A)氚同位素效应可用于评价标记的去甲肾上腺素与外周MAO-B的结合特异性；(B)在心、肺、肾和脾中可见MAO-B的显影和定量，而在肝脏中则不能；(C)除肝脏外，肾和心脏中MAO-B的活性最高；以及(D)与先前对脑的研究类似，在MAO-B含量较高的器官中使用11C-L-去丙烯基-D2可改善MAO-B的定量。这项研究表明，11C-L-异丙烯基-D2可用于测量不同变量的影响，包括烟草烟雾暴露对人体外周器官MAO B活性的影响。

UNLABELLED Monoamine oxidase (MAO) regulates neurotransmitter concentration in the brain and is also an important detoxifying enzyme in peripheral organs. It occurs in 2 subtypes, MAO A and MAO B. Their relative ratios in different organs are variable, depending on the particular organ and species, making it difficult to extrapolate measures from animals to humans. The purpose of this study was to investigate the feasibility of imaging MAO B in peripheral organs in humans with PET. METHODS Nine healthy subjects (7 males, 2 females; mean age +/- SD, 37 +/- 7 y) received 2 dynamic PET studies of the torso area 2 h apart with 11C-L-deprenyl and deuterium-substituted 11C-L-deprenyl (11C-L-deprenyl-D2). Time-activity curves for heart, lungs, liver, kidneys, and spleen and arterial plasma input were measured for each study. The uptake at plateau and the incorporation quotient (IQ = uptake/plasma input) as well as model terms K1 (which is a function of blood flow) and k3 and lambdak3 (which are kinetic terms proportional to MAO B) were compared to identify organs that showed reduced values with deuterium substitution (deuterium isotope effect) characteristic of MAO B. In addition, a sensitivity analysis compared the 2 tracers with respect to their ability to quantify MAO B. RESULTS Heart, lungs, kidneys, and spleen showed a robust deuterium isotope effect on uptake, IQ, k3, and lambdak3. The arterial plasma input function was significantly larger for 11C-L-deprenyl-D2 than for 11C-L-deprenyl. Liver time-activity curves were not affected by deuterium substitution and model terms could not be estimated. In organs showing an isotope effect, lambdak3 showed the rank order: kidneys >or= heart > lungs = spleen. A sensitivity analysis showed that 11C-L-deprenyl-D2 is a better index of MAO activity than 11C-L-deprenyl. CONCLUSION This study demonstrates that (a) the deuterium isotope effect is useful in assessing the binding specificity of labeled deprenyl to peripheral MAO B; (b) MAO B can be visualized and quantified in the heart, lungs, kidneys, and spleen but not in the liver; (c) with the exception of the liver, which cannot be measured, MAO B activity is highest in the kidneys and heart; and (d) quantitation in organs having high levels of MAO B is improved by the use of 11C-L-deprenyl-D2, similar to prior studies on the brain. This study indicates that 11C-L-deprenyl-D2 will be useful for measuring the effects of different variables, including tobacco smoke exposure on MAO B activity in peripheral organs in humans.

PET imaging of monoamine oxidase B in peripheral organs in humans.

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