Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation
Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation
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DOI：
10.1016/j.neuroimage.2007.11.011
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发表时间：
2008-03-01
期刊：
影响因子：
5.7
通讯作者：
Nnisa, Robert B.
中科院分区：
文献类型：
--
作者：
Fujita, Masahiro;Imaizumi, Masao;Nnisa, Robert B.
外周苯二氮卓类受体(PBR)在激活的小胶质细胞和巨噬细胞上表达上调，因此是一种有用的炎症生物标志物。我们开发了一种新的PET放射性配体[C-11]PBR28，它能够对健康猴子和中风大鼠的PBR进行成像和量化。本研究的目的是评价[C-11]PBR28定量测定健康受试者脑内PBRs的能力。12名受试者接受了120-180分钟的正电子发射计算机断层扫描，并连续采集动脉血浆，以测量未改变的母体放射性配基的浓度。进行了单组织和双组织的隔室分析。为了获得对分布体积的稳定估计，这是B-max/K-D和不可移位活动的总和，需要90分钟的脑成像。在人体内的分布体积仅为猴子的5%。这种相对较低的受体结合量需要两室模型，而不是一室模型，这表明与特定结合相比，非特异性结合是一个相当大的百分比。在12名受试者中，有两名的时间-活动曲线似乎没有PBR结合--即摄取的快速峰值和大脑的快速洗出。这些不寻常发现的原因(S)尚不清楚，但两名受试者也被发现与肺和肾脏等外围器官的PBR缺乏结合。总之，除了那些看起来没有PBR结合的受试者外，[C-11]PBR28是一种有希望的配基，用于量化PBR并定位与PBR密度增加相关的炎症。(C)2007 Elsevier Inc.保留所有权利。
The peripheral benzodiazepine receptor (PBR) is upregulated on activated microglia and macrophages and thereby is a useful biomarker of inflammation. We developed a novel PET radioligand, [C-11]PBR28, that was able to image and quantify PBRs in healthy monkeys and in a rat model of stroke. The objective of this study was to evaluate the ability of [C-11]PBR28 to quantify PBRs in brain of healthy human subjects. Twelve subjects had PET scans of 120 to 180 min duration as well as serial sampling of arterial plasma to measure the concentration of unchanged parent radioligand. One- and two-tissue compartmental analyses were performed. To obtain stable estimates of distribution volume, which is a summation of B-max/K-D and nondisplaceable activity, 90 min of brain imaging was required. Distribution volumes in human were only similar to 5% of those in monkey. This comparatively low amount of receptor binding required a two-rather than a one-compartment model, suggesting that nonspecific binding was a sizeable percentage compared to specific binding. The time-activity curves in two of the twelve subjects appeared as if they had no PBR binding-i.e., rapid peak of uptake and fast washout from brain. The cause(s) of these unusual findings are unknown, but both subjects were also found to lack binding to PBRs in peripheral organs such as lung and kidney. In conclusion, with the exception of those subjects who appeared to have no PBR binding, [C-11] PBR28 is a promising ligand to quantify PBRs and localize inflammation associated with increased densities of PBRs. (c) 2007 Elsevier Inc. All rights reserved.