Specific in vivo binding in the rat brain of [18F]RP 62203: a selective 5-HT2A receptor radioligand for positron emission tomography.
In vivo pharmacokinetic and brain binding characteristics of [18F]RP 62203, a selective high-affinity serotonergic 5-HT2A receptor antagonist, were assessed in the rat following intravenous injection of trace amount of the radioligand. The radioactive distribution profile observed in the brain 60 min after injection was characterized by greater than fourfold higher uptake in neocortex as compared to cerebellum (0.38 +/- 0.07% injected dose/g, % ID/g and 0.08 +/- 0.01 ID/g, respectively), consistent with in vivo specific binding to the 5-HT2A receptor. Furthermore, specific [18F]RP 62203 binding significantly correlated with the reported in vitro distribution of 5-HT2A receptors, but not with known concentration profiles of dopaminergic D2 or adrenergic alpha 1 receptors. Finally, detectable specific binding was abolished by pretreatment with large doses of ritanserin, a selective 5-HT2A antagonist, which resulted in uniform uptakes across cortical, striatal and cerebellar tissues. Thus, [18F]RP 62203 appears to be a promising selective tool to visualize and quantify 5-HT2A brain receptors in vivo with positron emission tomography.
Besret
L
L
CEA/DSV/DRIPP, Centre Cyceron, Caen, France.
Dauphin
F
F
Huard
C
C
Lasne
M C
MC
Vivet
R
R
Mickala
P
P
Barbelivien
A
A
Baron
J C
JC
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003499:Cyclic S-Oxides / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D009281:Naphthalenes / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D000319:Adrenergic beta-Antagonists; D003499:Cyclic S-Oxides; D005462:Fluorine Radioisotopes; D009281:Naphthalenes; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; C070475:fananserin