Synthesis and characterization of novel radiofluorinated probes for positron emission tomography imaging of monoamine oxidase B
Synthesis and characterization of novel radiofluorinated probes for positron emission tomography imaging of monoamine oxidase B
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用于单胺氧化酶 B 正电子发射断层扫描成像的新型放射性氟化探针的合成和表征
DOI：
10.1002/jlcr.3779
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发表时间：
2019
影响因子：
1.8
通讯作者：
Temma Takashi
中科院分区：
文献类型：
--
作者：
Yoshimoto Mitsuyoshi;Hirata Masahiko;Kagawa Shinya;Magata Yasuhiro;Ohmomo Yoshiro;Temma Takashi
单胺氧化酶B（MAO B）主要表达于神经胶质细胞，在神经递质调节中起重要作用，并且MAO B活性与多种神经元疾病有关。在这里，我们的目的是开发一种基于选择性MAO B抑制剂MD-230254结构的放射性氟化MAO B成像探针。我们合成了一系列化合物，并进行了体内外评价。合成了一系列MD-230254的氟化类似物，并评价了对MAO-B的抑制效力和选择性。以[18 F] CH 3COOF为原料，合成了5-[4-（2-[18 F]氟苄氧基）苯基]-3-（2-氰乙基）-1，3，4-恶二唑-2（3 H）-酮（2-[18 F]FBPO）。在有或无抑制剂预处理的雄性ddY小鼠中评价了静脉注射2-[18 F]FBPO后的生物分布。在合成和评价的化合物中，2-FBPO显示出与MD-230254相当的对MAO-B的高抑制效力和选择性。通过亲电反应成功地合成了2-[18F]FBPO，其放化纯度大于99%。2-[18 F]FBPO被大脑有效吸收，并显示出快速的血液清除，在注射后90分钟，大脑/血液放射性比为3.7。通过用MAO B选择性抑制剂预处理，脑放射性显著降低。2-[18 F]FBPO作为MAO B成像探针的巨大潜力，适用于各种疾病。
Monoamine oxidase B (MAO‐B), predominantly expressed in glial cells, plays an important role in neurotransmitter regulation, and MAO‐B activity relates to several neuronal diseases. Here, we aimed to develop a radiofluorinated MAO‐B imaging probe based on the structure of a selective MAO‐B inhibitor, MD‐230254. We synthesized and evaluated a series of compounds in vitro and in vivo. A series of fluorinated analogs of MD‐230254 were synthesized and evaluated for inhibitory potency and selectivity toward MAO‐B. 5‐[4‐(2‐[18F]Fluorobenzyloxy)phenyl]‐3‐(2‐cyanoethyl)‐1,3,4‐oxadiazol‐2(3H)‐one (2‐[18F]FBPO) was synthesized from a corresponding tributylstannyl precursor and [18F]CH3COOF. Biodistribution after intravenous injection of 2‐[18F]FBPO was evaluated in male ddY mice with or without pretreatment by inhibitors. Among the compounds synthesized and evaluated, 2‐FBPO showed high inhibitory potency and selectivity toward MAO‐B comparable with MD‐230254. 2‐[18F]FBPO was successfully synthesized by an electrophilic reaction with a high radiochemical purity of more than 99%. 2‐[18F]FBPO was efficiently taken up by the brain and showed rapid blood clearance, which provided a brain/blood radioactivity ratio of 3.7 at 90 minutes postinjection. The brain radioactivity was significantly decreased by pretreatment with an MAO‐B selective inhibitor. The great potential of 2‐[18F]FBPO as an MAO‐B imaging probe, applicable to a variety of diseases, is indicated.