Initial evaluation of [18F]F13714, a novel 5-HT1A receptor agonist in non-human primates - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2013

Initial evaluation of [18F]F13714, a novel 5-HT1A receptor agonist in non-human primates

Résumé

Aim. Brain serotonin 1A receptors (5-HT1A) exist in high- and low-affinity states. It is known that agonists bind preferentially to the high-affinity state of the receptors and therefore could provide a measure of the functional 5-HT1A receptors. Since all available fluorinated PET 5-HT1A radiopharmaceuticals are antagonists, it is of great interest to develop a fluorine-18 labelled agonist. [18F]F13714 is a novel ligand with high affinity (0.05 nM) for 5-HT1A receptors (J Nucl Med 2012; 53:969-976). Its nitro-precursor was synthesized and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiographies in rat brain and PETscans on rats and cats. With the Aim to prepare the transfer of this radiotracer in humans, we now report the first studies of [18F]F13714 in non-human primates. Materials and Methods. Four baseline PET studies, two blockade and one displacement studies with WAY-100635 (a 5-HT1A antagonist) were performed in two anaesthetized rhesus. Blood quantifications were done for each PET acquisition. Results and conclusion. The brain distribution of [18F]F13714 was consistent with 5-HT1A receptor distribution and confirmed data previously obtained in rodent and cat. No displacement was observed with WAY-100635 (1 mg/kg iv) but a blockade was observed when WAY100635 (1 mg/kg iv) was administered before the radiotracer. The blood profiles were reproducible between baselines acquisitions. The kinetic modelling using the two-tissue compartment model and k4=0 yielded the best results (i.e. lowest AIC and highest MSC). Test-retest of Ki was < 10%. In conclusion, if [18F]F13714 binds in vivo the high-affinity states of the 5-HT1A receptors, the modelling data and the competition studies suggest that it binds to the target in a quasi irreversible manner (ie very low k4), probably because of its particular high affinity.
Fichier non déposé

Dates et versions

hal-00948404 , version 1 (18-02-2014)

Identifiants

  • HAL Id : hal-00948404 , version 1

Citer

A. Tavares, G. Becker, O. Barret, T. Morley, D. Alagille, et al.. Initial evaluation of [18F]F13714, a novel 5-HT1A receptor agonist in non-human primates. Annual Congress of the European Association of Nuclear Medicine 2013, Oct 2013, Lyon, France. ⟨hal-00948404⟩
184 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More