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EVALUATING THE SPECIFICITY OF [18F]UCB-H FOR THE ISOFORM SV2A, COMPARED WITH ISOFORMS SV2B AND SV2C
Serrano Navacerrada, Maria Elisa; Aerts, Joël; Bahri, Mohamed Ali et al.
2016MedChem 2016 PET & Imaging : From Chemistry Lab to Clinical Applications
 

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Keywords :
SV2; 18F-UCB-H; competition assay; autoradiography; microPET
Abstract :
[en] Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the epilepsy (1, 2). [18F]UCB-H was developed like a tool to study the role of this isoform with neuroimaging techniques (3, 4). The objective of this study was to evaluate its specificity to this isoform comparing with the others, through a competition assay in rats with ex-vivo autoradiography and mPET imaging. Methods: Forty male Sprague-Dawley were used in ex-vivo autoradiography experiments (N=20) and in microPET imaging (N=20). Animals were pre-treated 30 minutes before the injection of [18F]UCB-H with a dose IP either of vehicle, Keppra (SV2A ligand), UCB068 (SV2B ligand) or UCB054 (SV2C ligand). Ex-vivo autoradiography was carried out 5 minutes after radiotracer injection while mPET images were acquiring with a dynamic scanner of 1 hour. Data were expressed in Standard Uptake Value and then, the area under the curve was calculated for the total process. Results: In ex-vivo autoradiography, ANOVA of two-ways showed statistical significant differences in brain uptake of [18F]UCB-H among the groups pretreated with Keppra or the ligand for SV2B and the control group. Regarding mPET data, statistical significant differences were found between the group injected with keppra and the rest of groups. Conclusion: Even if a considerable affinity between the ligands UCB068 and UCB054, and the receptor for the isoform SV2A exists, it is only detected during the first 5 minutes (ex-vivo technique), being certainly due to a nonspecific binding. This binding is not strong enough to show a direct competition with the radiotracer during a mPET acquisition. These results allow us to conclude that [18F]UCB-H is a suitable radiotracer for the imaging of the isoform SV2A in vivo, allowing us the clinical study about the molecular base of a disease with a high population impact, like the epilepsy.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Serrano Navacerrada, Maria Elisa ;  Université de Liège > Centre de recherches du cyclotron
Aerts, Joël ;  Université de Liège > Département de pharmacie > Département de pharmacie
Bahri, Mohamed Ali  ;  Université de Liège > Département de physique > Département de physique
Becker, Guillaume ;  Université de Liège > Centre de recherches du cyclotron
Giacomelli, Fabrice ;  Université de Liège > Centre de recherches du cyclotron
Lemaire, Christian ;  Université de Liège > Centre de recherches du cyclotron
Luxen, André ;  Université de Liège > Département de chimie (sciences) > Laboratoire de chimie organique de synthèse
Mercier, Joël;  UCB-Pharma
Mestdagh, Nathalie;  UCB-Pharma
Mievis, Frédéric ;  Université de Liège > Centre de recherches du cyclotron
Plenevaux, Alain  ;  Université de Liège > Département de chimie (sciences) > Département de chimie (sciences)
Salmon, Eric  ;  Université de Liège > Département des sciences cliniques > Neuroimagerie des troubles de la mémoire et révalid. cogn.
Warnier, Corentin
More authors (3 more) Less
Language :
English
Title :
EVALUATING THE SPECIFICITY OF [18F]UCB-H FOR THE ISOFORM SV2A, COMPARED WITH ISOFORMS SV2B AND SV2C
Publication date :
18 November 2016
Number of pages :
Poster
Event name :
MedChem 2016 PET & Imaging : From Chemistry Lab to Clinical Applications
Event organizer :
Société Royale de Chimie (SRC & KVCV) division Chimie Médicinale
Event place :
Mont-Saint-Guibert, Belgium
Event date :
18 novembre
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
since 28 March 2017

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