RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 164
OP 164
VO 51
IS supplement 2
A1 Jeih-San Liow
A1 Shuiyu Lu
A1 Sami Zoghbi
A1 Saurav Shrestha
A1 Robert Gladding
A1 Cheryl Morse
A1 Jussi Hirvonen
A1 Ramin Parsey
A1 Victor Pike
A1 Robert Innis
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/164.abstract
AB 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