Synthesis and biological evaluation in rat and cat of [18F]12ST05 as a potential 5-HT6 PET radioligand.
BACKGROUND
5-hydroxytryptamine (5-HT)6 receptors represent one of the more recently discovered serotoninergic receptor family. However, no 5-HT6 positron emission tomography (PET) radiotracer is currently used in clinical imaging studies. The purpose of this study was to propose the first fluorinated PET radiotracer for this brain receptor.


METHODS
A new compound presenting in vitro high affinity towards the serotoninergic 5-HT6 receptor, N-[2-(1-[(4-fluorophenyl)sulfonyl]-1H-indol-4-yloxy)ethyl]-N,N-dimethylamine, was labelled with fluorine 18 via a nitro-/fluoronucleophilic substitution. Biological evaluations included (i) in vitro and ex vivo autoradiographies in rat brain and (ii) a PET scan on anaesthetized cat.


CONCLUSIONS
Although the radioligand showed excellent brain penetration, it did not reveal any specific binding to the 5-HT6 receptors indicating that this radiotracer is not suitable for mapping 5-HT6 receptors using PET.
Tang
Sandrine
S
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR CNRS 5246, Université Lyon 1, Université de Lyon, Lyon, 69677 (Cermep), France.
Verdurand
Mathieu
M
Joseph
Benoît
B
Lemoine
Laëtitia
L
Daoust
Alexia
A
Billard
Thierry
T
Fournet
Guy
G
Le Bars
Didier
D
Zimmer
Luc
L
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002415:Cats; D007211:Indoles / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D008297:Male; D008657:Metabolic Clearance Rate; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D013449:Sulfonamides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D007211:Indoles; C526999:N-(2-(1-((4-fluorophenyl)sulfonyl)-1H-indol-4-yloxy)ethyl)-N,N-dimethylamine; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D013449:Sulfonamides; C097216:serotonin 6 receptor