Ginovart N, Hassoun W, Le Bars D, Weissmann D, Leviel V
CERMEP Cyclotron Unit, Lyon, France.
Synapse. 2000 Mar 1;35(3):192-200. doi: 10.1002/(SICI)1098-2396(20000301)35:3<192::AID-SYN4>3.0.CO;2-P.
The in vivo and ex vivo distributions and the pharmacological profile of the fluorinated phenylpiperazine derivative p-[(18)F]MPPF (4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-fluorobenzamido]-et hyl piperazine) were evaluated in the cat brain as a potential selective antagonist for 5-HT(1A) receptors using PET. After intravenous injection of p-[(18)F]MPPF in cats, there was a rapid accumulation of radioactivity in the brain, with 4% of the total radioactivity injected present in the brain at 4 minutes postinjection. The highest uptakes of radioactivity were observed in the hippocampus and cingulate cortex, regions known to be rich in 5-HT(1A) receptors, whereas lower levels of radioactivity were observed in the cerebellum. The mean ratio of radioactivity in the hippocampus to the cerebellum was 4.29 (SD = 0.21; n = 5) from 40 to 90 minutes postinjection of p-[(18)F]MPPF. The corresponding ratio for the cingulate cortex was 3.01 (SD = 0.16; n = 5). Specific binding in the hippocampus and the cingulate cortex was markedly reduced following injection of unlabeled WAY-100635 and pindolol but was unaffected by treatment with alpha1, 5-HT(2), or reuptake inhibitor agents indicating reversibility and selectivity of p-[(18)F]MPPF binding to 5-HT(1A) receptors. Ex vivo autoradiographic study with p-[(18)F]MPPF in cat brain sections showed labeling of areas rich in 5-HT(1A) receptors with a regional brain distribution that closely matched that observed using PET. These results indicate that p-[(18)F]MPPF may be a useful candidate for noninvasive PET imaging of 5-HT(1A) receptors in the living human brain.
使用正电子发射断层扫描（PET），在猫脑中评估了氟化苯基哌嗪衍生物对-[(18)F]MPPF（4-(2'-甲氧基苯基)-1-[2'-(N-2"-吡啶基)-对氟苯甲酰胺基]-乙基哌嗪）的体内和体外分布以及药理学特征，以确定其作为5-HT(1A)受体潜在选择性拮抗剂的可能性。在猫静脉注射对-[(18)F]MPPF后，放射性物质在脑中迅速蓄积，注射后4分钟时，脑中放射性物质占总注射放射性物质的4%。在海马体和扣带回皮质观察到最高的放射性摄取，已知这些区域富含5-HT(1A)受体，而在小脑中观察到较低水平的放射性。注射对-[(18)F]MPPF后40至90分钟，海马体与小脑放射性物质的平均比值为4.29（标准差=0.21；n=5）。扣带回皮质的相应比值为3.01（标准差=0.16；n=5）。注射未标记的WAY-100635和吲哚洛尔后，海马体和扣带回皮质的特异性结合明显降低，但用α1、5-HT(2)或再摄取抑制剂处理未受影响，表明对-[(18)F]MPPF与5-HT(1A)受体结合具有可逆性和选择性。用对-[(18)F]MPPF对猫脑切片进行的体外放射自显影研究显示，富含5-HT(1A)受体的区域有标记，其区域脑分布与PET观察到的情况密切匹配。这些结果表明，对-[(18)F]MPPF可能是用于活体人脑5-HT(1A)受体无创PET成像的有用候选物。
