Effect of cyclosporin A on the uptake of D3-selective PET radiotracers in rat brain.
Effect of cyclosporin A on the uptake of D3-selective PET radiotracers in rat brain.
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DOI：
10.1016/j.nucmedbio.2011.01.002
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发表时间：
2011-07
影响因子：
3.1
通讯作者：
Mach RH
中科院分区：
文献类型：
--
作者：
Tu Z;Li S;Xu J;Chu W;Jones LA;Luedtke RR;Mach RH
对 D3 与 D2 受体具有高亲和力和选择性的四种苯甲酰胺类似物用 11C 或 18F 进行放射性标记，用于体内评估。合成前体并对四种 D3 选择性苯甲酰胺类似物进行放射性标记。在对照大鼠和用环孢菌素 A 预处理的大鼠中评估了四种化合物的组织分布和脑摄取。环孢菌素 A 是 P-糖蛋白的调节剂和有助于血脑屏障的其他 ABC 外排转运蛋白的抑制剂。在对照和环孢素 A 预处理的大鼠中对 [11C]6 进行 MicroPET 成像。注射后 5 分钟和 30 分钟，所有四种化合物在对照大鼠中均显示出较低的脑摄取量；尽管最近报道了对类似物 6 (WC-10) 和 7 (WC-44) 进行的大鼠行为研究。给予环孢菌素 A 后，在静脉注射后 5 分钟和 30 分钟，所有四种 PET 放射性示踪剂均观察到脑摄取增加。注射。 microPET 研究中还观察到调节/抑制 ABC 转运蛋白后大脑摄取量增加。这些数据表明，含有 N-2-甲氧基苯基哌嗪部分的 D3 选择性构象灵活的苯甲酰胺类似物是在血脑屏障表达的 P-糖蛋白或其他 ABC 转运蛋白的底物，并且由于这些外排转运蛋白的作用，含有该药效基团的 PET 放射性示踪剂可能在啮齿动物中表现出低脑摄取。
Four benzamide analogs having a high affinity and selectivity for D3 versus D2 receptors were radiolabeled with 11C or 18F for in vivo evaluation. Precursors were synthesized and the four D3 selective benzamide analogs were radiolabeled. The tissue distribution and brain uptake of the four compounds were evaluated in control rats and rats pretreated with cyclosporin A, a modulator of P-glycoprotein and an inhibitor of other ABC efflux transporters that contribute to the blood brain barrier. MicroPET imaging was carried out for [11C]6 in a control and a cyclosporin A pre-treated rat. All four compounds showed low brain uptake in control rats at 5 and 30 min post-injection; despite recently reported rat behavioral studies conducted on analogs 6 (WC-10) and 7 (WC-44). Following administration of cyclosporin A, increased brain uptake was observed with all four PET radiotracers at both 5 and 30 min post-i.v. injection. An increase in brain uptake following modulation/inhibition of the ABC transporters was also observed in the microPET study. These data suggest that D3 selective conformationally-flexible benzamide analogs which contain a N-2-methoxyphenylpiperazine moiety are substrates for P-glycoprotein or other ABC transporters expressed at the blood-brain barrier, and that PET radiotracers containing this pharmacophore may display low brain uptake in rodents due to the action of these efflux transporters.
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影响因子：
3.4
作者：
Hocke, Carsten;Prante, Olaf;Gmeiner, Peter
通讯作者：
Gmeiner, Peter
影响因子：
4.1
作者：
Guigoni, C;Aubert, I;Bezard, E
通讯作者：
Bezard, E
影响因子：
7.3
作者：
Ghosh B;Antonio T;Zhen J;Kharkar P;Reith ME;Dutta AK
通讯作者：
Dutta AK
DOI：
10.1007/s00259-008-0832-z
发表时间：
2008-12-01
影响因子：
9.1
作者：
Lacan, Goran;Plenevaux, Alain;Melega, William P.
通讯作者：
Melega, William P.
DOI：
10.1111/j.1749-6632.1999.tb09291.x
发表时间：
1999-01-01
期刊：
ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA
影响因子：
--
作者：
Joyce, JN;Gurevich, EV
通讯作者：
Gurevich, EV