TY - JOUR T1 - Selectivity in rodents and monkeys of 11C-CUMI-101, an agonist radioligand for serotonin 5-HT1A receptors JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 164 LP - 164 VL - 51 IS - supplement 2 AU - Jeih-San Liow AU - Shuiyu Lu AU - Sami Zoghbi AU - Saurav Shrestha AU - Robert Gladding AU - Cheryl Morse AU - Jussi Hirvonen AU - Ramin Parsey AU - Victor Pike AU - Robert Innis Y1 - 2010/05/01 UR - http://jnm.snmjournals.org/content/51/supplement_2/164.abstract N2 - 164 Objectives 11C-CUMI-101 is an agonist radioligand for the serotonin subtype 1A (5-HT1A) receptor. Since some 5-HT1A receptor agonists also have significant affinity for alpha-1 adrenoceptors, we evaluated 11C-CUMI-101 in rodents and monkeys for potential binding to this alpha-1adrenoceptor. Methods Dynamic PET scans were acquired in male rats and male rhesus monkeys at baseline and after blockade of: 1) only 5-HT1A receptors using WAY 100635 (WAY); 0.5 mg/kg; 2) only alpha-1 adrenoceptors using prazosin; 2.0 mg/kg; and 3) both 5-HT1A and alpha-1 adrenoceptors using WAY plus prazosin. We performed 3 PET scans in rats and 4 in monkeys. Binding potential (BPND) was calculated using the cerebellum as the reference tissue. Results In rats, WAY incompletely blocked brain uptake of radioactivity in a region-dependent manner (BPND reduced by 25-75%). Prazosin significantly blocked (BPND reduced >70%) uptake in thalamus, which has a high density of alpha-1 receptors. WAY plus prazosin blocked uptake in all regions down to the level in cerebellum (BPND reduced > 80%). In monkeys, WAY reduced BPND by > 80% in all brain regions except thalamus (47%). Prazosin decreased BPND in monkey thalamus by 30% but had negligible effects in other regions with moderate to high densities of 5-HT1A receptors, including all neocortex, hippocampus, and amygdala. In these 5-HT1A receptor-rich regions, WAY plus prazosin displaced no greater amount than WAY alone. Conclusions 11C-CUMI-101 has significant binding to alpha-1 adrenoceptors in thalamus of rat and monkey brain. However, in the larger monkey brain, this receptor cross-reactivity was not measureable in regions with moderate to high densities of 5-HT1A receptors. Research Support The Intramural Research Program of NIMH supported this research (project # Z01-MH-002795-07). We thank PMOD Technologies (Zurich, Switzerland) for providing the image analysis software ER -