Perspectives on obesity imaging: [18F]2FNQ1P a specific 5-HT6 brain PET radiotracer

BackgroundEstimates suggest that approximatively 25% of the world population will be overweight in 2025. Better understanding of the pathophysiology of obesity will help to develop future therapeutics. Serotonin subtype 6 receptors (5-HT6) have been shown to be critically involved in appetite reduction and weight loss. However, it is not known if the pathological cascade triggered by obesity modifies the density of 5-HT6 receptors in the brain.MethodsInfluence of diet-induced obesity (DIO) in Wistar rats was explored using MRI (whole-body fat) and PET ([18F]2FNQ1P as a specific 5-HT6 radiotracer). The primary goal was to monitor the 5-HT6 receptor density before and after a 10-week diet (DIO group). The secondary goal was to compare 5-HT6 receptor densities between DIO group, Wistar control diet group, Zucker rats (with genetic obesity) and Zucker lean strain rats.ResultsWistar rats fed with high-fat diet showed higher body fat gain than Wistar control diet rats on MRI. [18F]2FNQ1P PET analysis highlighted significant clusters of voxels (located in hippocampus, striatum, cingulate, temporal cortex and brainstem) with increased binding after high-fat diet (p