2181 Age-related change in 5-HT6 receptor availability in healthy male volunteers measured with 11C-GSK215083 PET

• Published in: Journal of clinical and translational science Vol. 2; no. S1; pp. 3 - 4
• Main Authors: Radhakrishnan, Rajiv, Nabulsi, Nabeel, Gaiser, Edward, Gallezot, Jean-Dominique, Henry, Shannan, Planeta, Beata, Lin, Shu-fei, Ropchan, Jim, Williams, Wendol, Morris, Evan, D’Souza, Deepak Cyril, Huang, Yiyun, Carson, Richard E., Matuskey, David
• Format: Journal Article
• Language: English
• Published: Cambridge Cambridge University Press 01.06.2018
• Subjects: Age; Anxiety; Basic/Translational Science/Team Science; Cerebellum; Cognition; Cortex; Mental depression; Neostriatum; Pallidum (ventral); Population studies; Positron emission tomography; Putamen; Serotonin S2 receptors; Serotonin S6 receptors; Therapeutic applications
• ISSN: 2059-8661; 2059-8661
• DOI: 10.1017/cts.2018.44

OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate ( r =−0.41, p =0.03) (14% change per decade), and putamen ( r =−0.30, p =0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions ( r =−0.41, p =0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.