Comparison of 18F- and 11C-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography.
Comparison of 18F- and 11C-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography.
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DOI：
10.1007/s00259-010-1622-y
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发表时间：
2011-02
影响因子：
9.1
通讯作者：
Fujita, Masahiro
中科院分区：
文献类型：
--
作者：
Dickstein, Leah P.;Zoghbi, Sami S.;Fujimura, Yota;Imaizumi, Masao;Zhang, Yi;Pike, Victor W.;Innis, Robert B.;Fujita, Masahiro
转运蛋白（TSPO）是一种很有前途的神经炎症生物标志物。我们开发了两种新的PET配体，18F-PBR 06和11 C-PBR 28，以使TSPO成像。虽然我们先前的研究表明，这两种配体中的任何一种都可以用于定量人脑中的TSPO，但这些研究是在不同的受试者中进行的。在本研究中，我们直接比较了8名人类受试者中的18F-PBR 06和11 C-PBR 28，以确定（1）任一配体是否提供了更精确的TSPO测量值，以及（2）PBR 06与PBR 28相比更高的体外亲和力是否导致18F-PBR 06与11 C-PBR 28相比更高的体内结合。使用无约束双组织室模型，将体内结合计算为总分布容积（VT）。根据血浆游离分数（fP）校正VT，以基于脑中的游离配体浓度测量配体结合。两种配体以相似的精确度测量VT，如通过相似的良好可识别性所证明的。然而，两种放射性配体的VT随着数据采集长度的增加而增加，与脑中放射性代谢物的积累一致。尽管18F-PBR 06具有更高的亲脂性和更高的体外亲和力，但其VT/fP与11 C-PBR 28相似。18F-PBR 06和11 C-PBR 28在精密度、对放射性代谢物蓄积的敏感性和体内结合的幅度方面相似。因此，两种放射性配体之间的选择将主要由两种放射性核素的不同半衰期（110与20分钟）的后勤影响决定。
Translocator protein (TSPO) is a promising biomarker for neuroinflammation. We developed two new PET ligands, 18F-PBR06 and 11C-PBR28, to image TSPOs. Although our prior studies suggest that either of the two ligands could be used to quantify TSPOs in human brain, the studies were done in different sets of subjects. In this study, we directly compared 18F-PBR06 and 11C-PBR28 in eight human subjects to determine (1) whether either ligand provides more precise measurements of TSPOs and (2) whether the higher in vitro affinity of PBR06 compared to PBR28 led to higher in vivo binding of 18F-PBR06 compared to 11C-PBR28. In vivo binding was calculated as total distribution volume (VT), using an unconstrained two-tissue compartment model. VT was corrected for plasma free fraction (fP) to measure ligand binding based on free ligand concentration in brain. Both ligands measured VT with similar precision, as evidenced by similarly good identifiability. However, VT for both radioligands increased with increasing lengths of data acquisition, consistent with the accumulation of radiometabolites in brain. Despite its higher lipophilicity and higher in vitro affinity, VT/fP of 18F-PBR06 was similar to that of 11C-PBR28. Both 18F-PBR06 and 11C-PBR28 are similar in terms of precision, sensitivity to accumulation of radiometabolites, and magnitude of in vivo binding. Thus, selection between the two radioligands will be primarily determined by the logistical impact of the different half-lives of the two radionuclides (110 vs 20 min).
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DOI：
10.2967/jnumed.108.060186
发表时间：
2009-07
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Fujimura Y;Zoghbi SS;Simèon FG;Taku A;Pike VW;Innis RB;Fujita M
通讯作者：
Fujita M
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：
Imaizumi, Masao;Briard, Emmanuelle;Fujita, Masahiro
通讯作者：
Fujita, Masahiro
影响因子：
6.3
作者：
LASSEN, NA;BARTENSTEIN, PA;ANDERSEN, JV
通讯作者：
ANDERSEN, JV
影响因子：
9.3
作者：
Brown, Amira K.;Fujita, Masahiro;Innis, Robert B.
通讯作者：
Innis, Robert B.