References of "Gillard, Michel"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailEvaluation of [18F]UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain.
Warnock, Geoffrey; Aerts, Joël ULg; Bahri, Mohamed Ali ULg et al

in Journal of Nuclear Medicine (The) (2014), 55(8), 1336-1341

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 75 (26 ULg)
Full Text
Peer Reviewed
See detailH4 Histamine Receptors Mediate Cell Cycle Arrest in Growth Factor-Induced Murine and Human Hematopoietic Progenitor Cells
Petit-Bertron, Anne France; Machavoine, François; Defresne, Marie-Paule ULg et al

in PLoS ONE (2009), 4(8), 1-13

Detailed reference viewed: 41 (12 ULg)
Full Text
Peer Reviewed
See detailLocalization and photoaffinity labelling of the levetiracetam binding site in rat brain and certain cell lines
Fuks, Bruno; Gillard, Michel; Michel, Philippe et al

in European Journal of Pharmacology (2003), 478(1), 11-19

Levetiracetam (2S-(2-oxo-1-pyrrolidinyl)butanamide, KEPPRA(R)), a novel antiepileptic drug, has been shown to bind to a specific binding site located in the brain (Eur. J. Pharmacol. 286 (1995) 137). To ... [more ▼]

Levetiracetam (2S-(2-oxo-1-pyrrolidinyl)butanamide, KEPPRA(R)), a novel antiepileptic drug, has been shown to bind to a specific binding site located in the brain (Eur. J. Pharmacol. 286 (1995) 137). To identify the protein constituent of the levetiracetam binding site in situ, we synthesized the photoaffinity label [H-3]ucb 30889 ((2S)-2-[4-(3-azidophenyl)-2-oxopyrrolidin-1-yl]butanamide), a levetiracetam analog with higher affinity for the levetiracetam binding site. This radioligand was used to map the levetiracetam binding site within the brain and to study its cellular and subcellular distribution. Autoradiography experiments using [H-3]ucb 30889 in rat brain revealed a unique distribution profile that did not match that of classical receptors known to be involved in the generation of epileptic seizures. There was a high level of binding in the dentate gyrus, the superior colliculus, several thalamic nuclei, the molecular layer of the cerebellum and to a lesser extent in the cerebral cortex, the striatum and the hypothalamus. The levetiracetam binding site was restricted to neuronal cell types, undifferentiated PC 12 cells and was highly enriched in synaptic vesicles. [H-3]ucb 30889 was also used in photoaffinity labelling studies and shown to bind covalently to a membrane protein with a molecular weight of approximately 90 kDa. (C) 2003 Elsevier B.V. All rights reserved. [less ▲]

Detailed reference viewed: 57 (1 ULg)