[en] Synaptic vesicle 2 (SV2) proteins are critical to proper nervous system function and are involved in vesicle trafficking. The SV2A isoform has been identified as the binding site of the antiepileptic levetiracetam (LEV), making it an interesting therapeutic target for epilepsy. [18F]UCB-H is a novel PET imaging agent with a nanomolar affinity for human SV2A. Methods: preclinical PET studies were carried out in isoflurane anesthetized rats. Arterial input function was measured using an arteriovenous shunt and beta microprobe system. [18F]UCB-H was injected IV (140 ± 20 MBq bolus). Results: brain uptake of [18F]UCB-H was high, matching the expected homogeneous distribution of SV2A. The distribution volume (Vt) for [18F]UCB-H was calculated using Logan’s graphical analysis and the effect of LEV pretreatment on Vt measured. In control animals the mean whole-brain Vt was 9.76 ± 0.52 ml/cm3 (mean ± SD, n=4, test-retest), and the mean reproducibility in test-retest studies was 10.4 ± 6.5 %. Uptake of [18F]UCB-H was dose-dependently blocked by pretreatment with LEV (0.1 - 100 mg/kg IV).
Conclusion: our results indicate that [18F]UCB-H is a suitable radiotracer for the imaging of SV2A in vivo. This is the first PET tracer for in vivo quantification of SV2A. The necessary steps for implementation of [18F]UCB-H production under GMP conditions and first in human studies are planned.
Research Center/Unit :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Warnock, Geoffrey
Aerts, Joël ; Université de Liège - ULiège > Centre de recherches du cyclotron
Bahri, Mohamed Ali ; Université de Liège - ULiège > Centre de recherches du cyclotron
Bretin, Florian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Lemaire, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Giacomelli, Fabrice ; Université de Liège - ULiège > Centre de recherches du cyclotron
Mievis, Frédéric ; Université de Liège - ULiège > Centre de recherches du cyclotron
Mestdagh, Nathalie; UCB Pharma
Buchanan, Tim; UCB Pharma
Valade, Anne; UCB Pharma
Mercier, Joël; UCB Pharma
Wood, Martyn; UCB Pahrma
Gillard, Michel; UCB Pharma
Seret, Alain ; Université de Liège - ULiège > Département de physique > Imagerie médicale expérimentale
Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse
SALMON, Eric ; Centre Hospitalier Universitaire de Liège - CHU > Neurologie Sart Tilman
Plenevaux, Alain ; Université de Liège - ULiège > Centre de recherches du cyclotron
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
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