Autoradiographic Evaluation of [F-18]FECUMI-101, a High Affinity 5-HT1AR Ligand in Human Brain

作者：Kumar J S Dileep^*; Underwood Mark D; Simpson Norman R; Kassir Suham A; Prabhakaran Jaya; Majo Vattoly J; Bakalian Mihran J; Parsey Ramin V; Mann J John; Arango Victoria

来源：ACS Medicinal Chemistry Letters, 2016, 7(5): 482-486.

DOI：10.1021/acsmedchemlett.5b00499

• 5-HT1AR
• alpha R-1
• radiotracer
• autoradiography
• PET
• hippocampus

[F-18]EECUMI-101 ([F-18]1) is a 5HT(1A)R ligand demonstrating specific binding in brain regions corresponding to the distribution of 5-HT1AR in baboons. However, we detected moderate uptake of [F-18]1 in baboon thalamus, a brain region lacking 5-HT1AR We sought to investigate the relative binding of [F-18]1 to 5-HT1AR, alpha R-1, and 5-HT7R in vitro. Using autoradiography in human brain sections, specific binding of [F-18)1 to 5-HT1AR was confirmed. However, [F-18]1 also showed 26% binding to alpha R-1 in PFC. The hippocampal formation exhibited 51% and 92% binding of [F-18]1 to alpha R-1 and 5-HT1AR, respectively. Thalamus and cerebellum showed very little binding. There is no measurable specific binding of [F-18]1 to 5-HT7R and no effect of temperature on [F-18]1 specific binding to 5-HT1AR or alpha R-1 These results indicate that, while [F-18]FECUMI-101 is not a completely selective 5-HT1AR ligand for receptor quantification, it may be useful for occupancy measurements of drugs acting at 5-HT1AR in vivo.

• 出版日期2016-5