Passchier J, van Waarde A, Pieterman R M, Elsinga P H, Pruim J, Hendrikse H N, Willemsen A T, Vaalburg W
PET Center, Groningen University Hospital, The Netherlands.
J Nucl Med. 2000 Nov;41(11):1830-5.
Serotonin-1A (5-hydroxytryptamine-1A [5-HT1A]) receptors have been reported to play an important role in the pathophysiology of a variety of psychiatric and neurodegenerative disorders. Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2'-pyridinyl)-p-[18F]fluorobenzamido ]ethylpiperazine ([18F]MPPF) may be suitable for 5-HT1A receptor imaging in humans. The aim of this study was to determine if [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor densities in brain regions of healthy human volunteers.
[15O]H2O perfusion scanning was performed before intravenous injection of [18F]MPPF to obtain anatomic information. Cerebral radioactivity was monitored using a PET camera. Plasma metabolites of [18F]MPPF were determined by high-performance liquid chromatography. Binding potentials were calculated using the metabolite-corrected arterial input function and a linear graphic method (Logan-Patlak analysis).
The highest levels of radioactivity were observed in the medial temporal cortex, especially in the hippocampal area. In contrast, the cerebellum and basal ganglia showed low uptake of 18F, in accordance with known 5-HT1A receptor distribution. The calculated binding potentials correlated well with literature values for 5-HT1A receptor densities. The binding potentials for [18F]MPPF were 4-6 times lower than those that have been reported for [carbonyl-1C]-(N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyrid yl) cyclohexane-carboxamide (WAY 100635), indicating that [18F]MPPF has a lower in vivo affinity for 5-HT1A receptors.
These results confirm that [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor distribution in the living human brain. The rapid dissociation from the receptor makes this ligand a possible candidate to monitor changes in endogenous serotonin levels.
据报道，5-羟色胺1A（5-hydroxytryptamine-1A [5-HT1A]）受体在多种精神疾病和神经退行性疾病的病理生理学中发挥重要作用。动物实验表明，4-(2'-甲氧基苯基)-1-[2'-(N-2'-吡啶基)-p-[18F]氟苯甲酰胺基]乙基哌嗪（[18F]MPPF）可能适用于人体5-HT1A受体成像。本研究的目的是确定[18F]MPPF是否可用于定量分析健康人类志愿者脑区中5-HT1A受体密度。
在静脉注射[18F]MPPF前进行[15O]H2O灌注扫描以获取解剖学信息。使用正电子发射断层显像仪监测脑放射性。通过高效液相色谱法测定[18F]MPPF的血浆代谢物。使用代谢物校正的动脉输入函数和线性图像法（洛根-帕特拉克分析）计算结合势。
在内侧颞叶皮质，尤其是海马区观察到最高放射性水平。相比之下，根据已知的5-HT1A受体分布，小脑和基底神经节对18F摄取较低。计算得到的结合势与5-HT1A受体密度的文献值相关性良好。[18F]MPPF的结合势比已报道的[羰基-1C]-(N-(2-(4-(2-甲氧基苯基)-1-哌嗪基)乙基)-N-(2-吡啶基)环己烷-甲酰胺（WAY 100635）低4至6倍，表明[18F]MPPF在体内对5-HT1A受体的亲和力较低。
这些结果证实[18F]MPPF可用于定量分析活体人脑内5-HT1A受体分布。该配体与受体的快速解离使其成为监测内源性5-羟色胺水平变化的可能候选物。
