Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30329, United States.
Bioorg Med Chem Lett. 2013 Oct 1;23(19):5415-20. doi: 10.1016/j.bmcl.2013.07.045. Epub 2013 Jul 30.
The compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4-yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-one (1) was synthesized and positively evaluated in vitro for high potency and selectivity with human oxytocin receptors. The positron emitting analogue, [F-18]1, was synthesized and investigated in vivo via PET imaging using rat and cynomolgus monkey models. PET imaging studies in female Sprague-Dawley rats suggested [F-18]1 reached the brain and accumulated in various regions of the brain, but washed out too rapidly for adequate quantification and localization. In vivo PET imaging studies in a male cynomolgus monkey suggested [F-18]1 had limited brain penetration while specific uptake of radioactivity significantly accumulated within the vasculature of the cerebral ventricles in areas representative of the choroid plexus.
1-(1-(2-(2-(2-氟乙氧基)-4-(哌啶-4-基氧基)苯基)乙酰基)哌啶-4-基)-3,4-二氢喹啉-2(1H)-酮（1）被合成，并对其与人催产素受体的高活性和选择性进行了体外积极评价。正电子发射类似物[F-18]1 被合成，并通过使用大鼠和食蟹猴模型的 PET 成像进行了体内研究。在雌性 Sprague-Dawley 大鼠中的 PET 成像研究表明[F-18]1 到达大脑并在大脑的各个区域积累，但由于定量和定位不足，清除过快。在雄性食蟹猴中的体内 PET 成像研究表明[F-18]1 的脑穿透能力有限，而放射性摄取物的特异性在代表脉络丛的脑室内血管区域内显著积累。
