Single-step high-yield radiosynthesis and evaluation of a sensitive 18F-labeled ligand for imaging brain peripheral benzodiazepine receptors with PET.
Single-step high-yield radiosynthesis and evaluation of a sensitive 18F-labeled ligand for imaging brain peripheral benzodiazepine receptors with PET.
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DOI：
10.1021/jm8011855
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发表时间：
2009-02-12
影响因子：
7.3
通讯作者：
Pike VW
中科院分区：
文献类型：
--
作者：
Briard E;Zoghbi SS;Siméon FG;Imaizumi M;Gourley JP;Shetty HU;Lu S;Fujita M;Innis RB;Pike VW
外周苯二氮卓受体（PBR）水平升高与小胶质细胞对炎症反应的活化相关。因此，体内PBR成像对于研究脑炎症状况是有价值的。用于正电子发射断层扫描（PET）成像的灵敏、容易制备和容易获得的放射性配体对于该目的是期望的。我们描述了一种新的18F标记的PBR放射性配体，即[18F] N-氟乙酰基-N-（2，5-二甲氧基苄基）-2-苯氧基苯胺（[18F]9）。[18 F]9通过单一且高效的步骤容易地产生，[18 F]氟离子与相应的溴前体8的反应。配体9在体外表现出对PBR的高亲和力。PET显示，[18 F]9被贪婪地摄取到猴脑中，并产生高比例的PBR特异性与非特异性结合。[18 F]9在大鼠和猴中没有去甲肾上腺素，主要产生极性放射性代谢物。在大鼠中，一种中等亲脂性的低水平放射性代谢物被鉴定为[18 F]2-氟-N-（2-苯氧基苯基）乙酰胺（[18 F]11）。[18 F]9是一种有前途的放射性配体，用于未来在活体人脑中进行PBR成像。
Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with activated microglia in their response to inflammation. Hence, PBR imaging in vivo is valuable for investigating brain inflammatory conditions. Sensitive, easily prepared and readily available radioligands for imaging with positron emission tomography (PET) are desirable for this purpose. We describe a new 18F-labeled PBR radioligand, namely [18F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([18F]9). [18F]9 was produced easily through a single and highly efficient step, the reaction of [18F]fluoride ion with the corresponding bromo precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that [18F]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific to nonspecific binding. [18F]9 was devoid of defluorination in rat and monkey and gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite of intermediate lipophilicity was identified as [18F]2-fluoro-N-(2-phenoxyphenyl)acetamide ([18F]11). [18F]9 is a promising radioligand for future imaging of PBR in living human brain.
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影响因子：
5.7
作者：
Imaizumi, Masao;Briard, Emmanuelle;Fujita, Masahiro
通讯作者：
Fujita, Masahiro
影响因子：
5.8
作者：
Chelli, B;Lena, A;Martini, C
通讯作者：
Martini, C
影响因子：
9.3
作者：
Brown, Amira K.;Fujita, Masahiro;Innis, Robert B.
通讯作者：
Innis, Robert B.
影响因子：
3.8
作者：
GANDELMAN, MS;BALDWIN, RM;INNIS, RB
通讯作者：
INNIS, RB
影响因子：
5.7
作者：
Fujita, Masahiro;Imaizumi, Masao;Nnisa, Robert B.
通讯作者：
Nnisa, Robert B.