Quantification of translocator protein (18 kDa) in the human brain with PET and a novel radioligand, (18)F-PBR06.
Quantification of translocator protein (18 kDa) in the human brain with PET and a novel radioligand, (18)F-PBR06.
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DOI：
10.2967/jnumed.108.060186
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Fujita M
中科院分区：
文献类型：
--
作者：
Fujimura Y;Zoghbi SS;Simèon FG;Taku A;Pike VW;Innis RB;Fujita M
转运蛋白（TSPO）（18 kDa），以前称为外周苯二氮卓受体，在活化的小胶质细胞和巨噬细胞上上调，因此是炎症的生物标志物。我们以前报道过，11 C标记的芳氧基苯胺（半衰期，20分钟）能够量化TSPO在健康人脑。由于许多PET中心将受益于更长寿命的18F标记的放射性配体（半衰期，110 min），因此本研究的目的是评价密切相关的芳氧基苯胺（18F-N-氟乙酰基-N-（2，5-二甲氧基苄基）-2-苯氧基苯胺[18F-PBR 06]）定量健康人脑中TSPO的能力。共9名人类受试者注射18F-PBR 06（~185 MBq）并扫描5小时，在相机外休息。在动脉血浆中测量从放射性代谢产物中分离的18F-PBR 06的浓度。局部脑和血浆数据的建模表明，2-组织房室模型上级1-组织房室模型。即使所有时间点的数据都用于拟合，用PET测量的脑活动浓度也始终大于晚期（280-300分钟）的建模值，但不是早期时间点的建模值。较大的值可能是由于放射性代谢物在大脑中缓慢积累所致。为了确定更准确测量分布容积（VT）的适当时间，VT是受体结合和不可置换活性的总和，我们研究了扫描持续时间与最大或接近最大可识别性相关。我们发现，120分钟的扫描提供了最佳的VT识别率（~2%）。图像显示无明显的退化。18F-PBR 06可以使用120分钟的图像采集和血浆中放射性配体的同时测量来量化健康人脑中的TSPO。尽管大脑活动可能受到放射性代谢物的污染，但污染百分比被认为很小（<10%），因为分布体积值在60-120分钟内保持稳定，变化小于10%。18F-PBR 06是11 C标记的放射性配体的更长寿命和有前途的替代品，用于测量TSPO作为大脑中炎症的生物标志物。
Translocator protein (TSPO) (18 kDa), formerly called the peripheral benzodiazepine receptor, is upregulated on activated microglia and macrophages and is, thus, a biomarker of inflammation. We previously reported that an 11C-labeled aryloxyanilide (half-life, 20 min) was able to quantify TSPOs in the healthy human brain. Because many PET centers would benefit from a longer-lived 18F-labeled radioligand (half-life, 110 min), the objective of this study was to evaluate the ability of a closely related aryloxyanilide (18F-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline [18F-PBR06]) to quantify TSPOs in the healthy human brain. A total of 9 human subjects were injected with 18F-PBR06 (~185 MBq) and scanned for 5 h, with rest periods outside the camera. The concentrations of 18F-PBR06, separated from radiometabolites, were measured in arterial plasma. Modeling of regional brain and plasma data showed that a 2-tissue-compartment model was superior to a 1-tissue-compartment model. Even if data for all time points were used for the fitting, concentrations of brain activity measured with PET were consistently greater than the modeled values at late (280–300 min) but not at early time points. The greater values may have been caused by the slow accumulation of radiometabolites in the brain. To determine an adequate time for more accurate measurement of distribution volume (VT), which is the summation of receptor binding and nondisplaceable activity, we investigated which scan duration would be associated with maximal or near-maximal identifiability. We found that a scan of 120 min provided the best identifiability of VT (~2%). The images showed no significant defluorination. 18F-PBR06 can quantify TSPOs in the healthy human brain using 120 min of image acquisition and concurrent measurements of radioligand in plasma. Although brain activity is likely contaminated with radiometabolites, the percentage contamination is thought to be small (<10%), because values of distribution volume are stable during 60–120 min and vary by less than 10%. 18F-PBR06 is a longer-lived and promising alternative to 11C-labeled radioligands to measure TSPOs as a biomarker of inflammation in the brain.
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影响因子：
14.5
作者：
LEENDERS, KL;PERANI, D;JONES, T
通讯作者：
JONES, T
影响因子：
3.1
作者：
Waterhouse, Rikki N
通讯作者：
Waterhouse, Rikki N
影响因子：
7.3
作者：
Briard E;Zoghbi SS;Siméon FG;Imaizumi M;Gourley JP;Shetty HU;Lu S;Fujita M;Innis RB;Pike VW
通讯作者：
Pike VW
影响因子：
5.7
作者：
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通讯作者：
Fujita, Masahiro
影响因子：
3.8
作者：
DOBLE, A;MALGOURIS, C;LEFUR, G
通讯作者：
LEFUR, G