In vivo evaluation of radioiodinated 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)-piperazine derivatives as new ligands for sigma receptor imaging using single photon emission computed tomography.
In vivo evaluation of radioiodinated 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)-piperazine derivatives as new ligands for sigma receptor imaging using single photon emission computed tomography.
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DOI：
10.1248/bpb.29.2009
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发表时间：
2006-10
影响因子：
2
通讯作者：
M. Hirata;Tetsuya Mori;Seigo Soga;T. Umeda;Y. Ohmomo
中科院分区：
文献类型：
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作者：
M. Hirata;Tetsuya Mori;Seigo Soga;T. Umeda;Y. Ohmomo
新系列放射性碘标记的1-[2-(3，4-dimethoxyphenyl)ethyl]-4-[3-(2-iodophenyl)propyl]piperazine类似物(o-Bon)和1-[2-(3，4-dimethoxyphenyl)ethyl]-4-[3-(3-iodophenyl)propyl]piperazine(m-Bon)被评价为单光子发射计算机断层扫描(SPECT)放射性药物，用于定位中枢神经系统(CNS)和周围器官的Sigma受体。[125I]o-和m-Bon在小鼠体内的生物分布研究表明，[125I]o-和m-Bon在大脑中的初始摄取量和长期滞留时间都很高。与大脑的高摄取率和储留率相比，血液积累较低，导致良好的脑血比(7.9-9.2)。在其他组织中，肝、肾、心、肺和胰腺对~(125)I]o-和m-Bon的摄取较高。此外，[125I]o-和m-Bon与Sigma受体的选择性相互作用也被不同的Sigma和其他受体配体的预处理实验所证实。氟哌啶醇处理后，[~(125)I]O-和m-Bon的蓄积减少。这些数据表明，[125I]o-和m-Bon与Sigma受体的结合是可逆的和竞争性的。此外，在大鼠的体外放射自显影中，[125I]o-和m-Bon在顶叶皮质、前庭核和脑桥核有高摄取，在丘脑、下丘、海马体、下丘脑和颞叶皮质有中等摄取。这些体外放射自显影与Sigma受体的组织化学分布相似。此外，摄取~(125)I]o-和m-Bon反映了大脑中Sigma受体的数量。这些结果表明，放射性标记的o-Bon和m-Bon具有良好的SPECT示踪中枢和外周器官中的Sigma受体的特性。
New series of radioiodinated analogues of 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-[3-(2-iodophenyl)propyl]piperazine (o-BON) and 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-[3-(3-iodophenyl)propyl]piperazine (m-BON) were evaluated as single photon emission computed tomography (SPECT) radiopharmaceuticals for mapping sigma receptors in the central nervous system (CNS) and peripheral organs. In vivo biodistribution studies of [125I] o- and m-BON in mice demonstrated high initial uptakes and prolonged retention in the brain. In contrast to high brain uptake and retention, the blood accumulations were low, resulting in good brain-blood ratios (7.9-9.2). In the other tissues, high uptake of [125I] o- and m-BON were observed in the liver, kidney, heart, lung, and pancreas. Moreover, selective interactions of [125I] o- and m-BON with sigma receptors were confirmed by pretreatment experiments with various sigma and other receptor ligands. Haloperidol posttreatment induced decreases in the accumulation of [125I] o- and m-BON. These data suggest that [125I] o- and m-BON binding to sigma receptors is reversible and competitive. Furthermore, ex vivo autoradiograms of [125I] o- and m-BON in rats showed high uptake in the parietal cortex, vestibular nucleus, and pons nucleus and moderate uptake in the thalamus, inferior colliculus, hippocampus, hypothalamus, and temporal cortex. These ex vivo autoradiograms were comparable with the histochemical distribution of sigma receptors. Furthermore, the uptake of [125I] o- and m-BON reflected quantitative amounts of sigma receptor in the brain. These results demonstrated that radiolabeled o- and m-BON have good characteristics for mapping sigma receptors in the CNS and the peripheral organs with SPECT.