Brain and whole-body imaging in nonhuman primates of [11C]PBR28, a promising PET radioligand for peripheral benzodiazepine receptors
Brain and whole-body imaging in nonhuman primates of [11C]PBR28, a promising PET radioligand for peripheral benzodiazepine receptors
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DOI：
10.1016/j.neuroimage.2007.09.063
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发表时间：
2008-02-01
期刊：
影响因子：
5.7
通讯作者：
Fujita, Masahiro
中科院分区：
文献类型：
--
作者：
Imaizumi, Masao;Briard, Emmanuelle;Fujita, Masahiro
目的：外周苯二氮卓受体（PBRs）在活化的小胶质细胞上上调，因此是神经炎症的生物标志物。我们开发了一种具有芳氧基苯胺结构的PET配体，[O-甲基-C-11] N-乙酰基-N-（2-甲氧基苄基）-2-苯氧基-5-吡啶胺（[C-11] PBR 28），以使PBRs成像。本研究的目的是评价恒河猴脑摄取的动力学，以及外周结合对动脉输入功能的影响。（基线：n=6，阻断：n=1）和全身PET成像（基线：n=3，阻断：n=1）的[C-11] PBR 28在全脑和两次全身扫描中进行放射性代谢物校正的动脉输入功能测量。饱和剂量的非放射性PBR配体通过从外周器官中的PBR中置换放射性配体，在2分钟时显著增加血浆（类似于400%增加）和脑（类似于200%）中的[C-11] PBR 28。在基线扫描中，放射性脑摄取在注射[C-11] PBR 28后40 min达到峰值，并且较高（与300%标准化摄取值相似）。图像显示没有可用于参考组织分析的无受体区域。因此，受体密度的定量需要测量动脉血浆中的母体放射性配体。根据阻断扫描估计不可置换摄取，仅与基线条件下测量的总分布体积的5%相似。[C-11] PBR 28的分布体积在110 min内稳定测定。结论：[C-11] PBR 28在猴脑中的局部摄取可定量为与受体密度成正比的值，即平衡分布体积。[C-11] PBR 28在脑中具有高水平的特异性结合，应提供PBRs变化的灵敏测量。爱思唯尔公司出版
Objectives: Peripheral benzodiazepine receptors (PBRs) are upregulated on activated microglia and are thereby biomarkers of neuroinflammation. We developed a PET ligand with an aryloxyanilide structure, [O-methyl-C-11]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine ([C-11]PBR28), to image PBRs. The objectives of the current study were to evaluate kinetics of brain uptake, and the influence of the peripheral binding on the arterial input function in rhesus monkey.Methods: Brain (baseline: n=6, blocking: n=1) and whole-body PET imaging (baseline: n=3, blocking: n=1) of [C-11]PBR28 were performed with the measurement of radio metabolite-corrected arterial input function in all brain and two whole body scans.Results: Saturating doses of nonradioactive PBR ligands markedly increased [C-11]PBR28 in plasma (similar to 400% increase) and brain (similar to 200%) at 2 min by displacing radioligand from PBRs in peripheral organs. Brain uptake of radioactivity peaked in baseline scans at similar to 40 min after injection of [C-11]PBR28 and was high (similar to 300% standardized uptake value). The images showed no receptor-free region that could be used for reference tissue analysis. Thus, quantitation of receptor density required measurement of parent radioligand in arterial plasma. Nondisplaceable uptake was estimated from the blocked scans and was only similar to 5% of total distribution volume measured under baseline conditions. Distribution volume of [C-11]PBR28 was stably determined within 110 min of scanning.Conclusions: Regional brain uptake of [C-11]PBR28 in monkey could be quantified as a value proportional to the density of receptors-namely, as equilibrium distribution volume. [C-11]PBR28 had high levels of specific binding in brain and should provide a sensitive measure of changes in PBRs. Published by Elsevier Inc.