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Background. Serotonin is an important chemical messenger (i.e., neurotransmitter) in brain and plays important roles in regulation of mood, appetite, and sleep. Furthermore, the mechanism of many antidepressant medications is to increase serotonin transmission in brain. We developed a new probe for one of serotonin's receptors – the 5-HT1A receptor. This radioligand shows good uptake in monkey brain in regions with high densities of receptors. We are now studying this tracer in human subjects. See references below.
Legend. Uptake of [11C](R)-(-)-RWAY in rhesus brain.
A) PET images (middle) were summed from 30 – 90 min. The corresponding MR images are on left, and the fused PET and MR images are on right.
B) Time course of regional brain activities after injection of [11C](R)-(-)-RWAY. Activity is shown as %SUV (standard uptake value) which normalizes for injected dose and body weight. %SUV = (% injected activity / cm3 tissue) * (g body weight). Cerebellum (Filled circle); Prefrontal cortex (Triangle); Lateral temporal cortex (Diamond); Dorsal raphe (Square); and Medial temporal region (X).
References. 1) F. Yasuno, S. Zoghbi, J. McCarron, M. Ichise, A. Brown, J. Hong, R. Gladding, J. Bacher, V.W. Pike, and R.B. Innis. Quantification of serotonin 5-HT1A receptors in monkey brain with [11C](R)-( )RWAY. Synapse, 60: 510-520, 2006.
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2) J.S. Liow, S. Lu, J. McCarron, J. Hong, J. Musachio, V.W. Pike, R.B. Innis, and S.S. Zoghbi. Effect of P-glycoprotein inhibitor, Cyclosporine A, on the disposition in rodent brain and blood of the 5-HT1A receptor radioligand [11C](R)-(-)RWAY. Synapse, 61: 96-105, 2007.
3) X.-Y. Zhang, F. Yasuno, J.A. McCarron, S.S. Zoghbi, J.-S. Liow, J. Hong, J.A. McCarron, V.W. Pike, and R.B. Innis. Quantification of serotonin 5-HT1A receptors in humans with [11C](R)-(-)-RWAY: Radiometabolite(s) likely confound brain measurements. Synapse. 61: 469-477, 2007.
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