Ca. Mathis et al., [C-11] WAY-100635 - A RADIOLIGAND FOR IMAGING 5-HT1A RECEPTORS WITH POSITRON EMISSION TOMOGRAPHY, Life sciences, 55(20), 1994, pp. 161200403-161200407
Citations number
15
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
The potent and selective 5-HT1A antagonist WAY 100635 azinyl]ethyl]-N-
(2-pyridinyl)clohexanecarboxamide) was radiolabeled with C-11 in high
specific activity, and the in vivo properties of this radioligand were
assessed in the brains of rats and monkeys. Following i.v. tail vein
injection in rats, [C-11]WAY 100635 rapidly penetrated into brain tiss
ue and was retained over a 30-90 min time period in a manner consisten
t with the known distribution of 5-HT1A receptors. Pretreatment of rat
s with the selective 5-HT1A agonist (+/-)-8-OH-DPAT effectively blocke
d the retention of radioactivity in brain regions known to contain hig
h densities of 5-HT1A receptors. The hippocampus-to-cerebellum radioac
tivity concentration ratio reached a maximum of 16:1 at 60 min post in
jection. Following i.v. injection of [C-11]WAY 100635 in rhesus monkey
s, the concentrations of radioactivity in brain regions were consisten
t with the reported distribution of 5-HT1A receptors in primates, and
the frontal cortex-to-cerebellum ratio reached 5.5:1 at 80 min post in
jection. Pretreatment of the monkeys with (+/-)-8-OH-DPAT reduced this
ratio to 1.4:1, and injection of (+/-)-8-OH-DPAT 20 min after the inj
ection of [C-11]WAY100635 significantly displaced frontal cortex bindi
ng. The in vivo properties of [C-11]WAY 100635 in rats and monkeys str
ongly support the future utility of this radioligand for imaging 5-HT1
A receptors using positron emission tomography (PET).