Evaluating the In Vivo Specificity of [ 18 F]UCB-H for the SV2A Protein, Compared with SV2B and SV2C in Rats Using microPET.

Autor: Serrano ME; GIGA-CRC In Vivo Imaging, University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. meserrano@uliege.be., Becker G; GIGA-CRC In Vivo Imaging, University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. guillaume.becker@sckcen.be., Bahri MA; GIGA-CRC In Vivo Imaging, University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. M.Bahri@uliege.be., Seret A; GIGA-CRC In Vivo Imaging, University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. aseret@uliege.be., Mestdagh N; UCB Pharma s.a., 1420 Braine-l'Alleud, Belgium. Nathalie.Mestdagh@ucb.com., Mercier J; UCB Pharma s.a., 1420 Braine-l'Alleud, Belgium. joel.mercier@ucb.com., Mievis F; Nucleis s.a., University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. frederic.mievis@nucleis.eu., Giacomelli F; Nucleis s.a., University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. fabrice.giacomelli@nucleis.eu., Lemaire C; GIGA-CRC In Vivo Imaging, University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. Christian.Lemaire@uliege.be., Salmon E; GIGA-CRC In Vivo Imaging, University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. Eric.Salmon@uliege.be., Luxen A; GIGA-CRC In Vivo Imaging, University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. aluxen@uliege.be., Plenevaux A; GIGA-CRC In Vivo Imaging, University of Liège, 8 Allée du 6 Août, Building B30, Sart Tilman, 4000 Liège, Belgium. alain.plenevaux@uliege.be.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2019 May 01; Vol. 24 (9). Date of Electronic Publication: 2019 May 01.
DOI: 10.3390/molecules24091705
Abstrakt: The synaptic vesicle protein 2 (SV2) is involved in synaptic vesicle trafficking. The SV2A isoform is the most studied and its implication in epilepsy therapy led to the development of the first SV2A PET radiotracer [ 18 F]UCB-H. The objective of this study was to evaluate in vivo, using microPET in rats, the specificity of [ 18 F]UCB-H for SV2 isoform A in comparison with the other two isoforms (B and C) through a blocking assay. Twenty Sprague Dawley rats were pre-treated either with the vehicle, or with specific competitors against SV2A (levetiracetam), SV2B (UCB5203) and SV2C (UCB0949). The distribution volume (Vt, Logan plot, t* 15 min) was obtained with a population-based input function. The Vt analysis for the entire brain showed statistically significant differences between the levetiracetam group and the other groups ( p < 0.001), but also between the vehicle and the SV2B group ( p < 0.05). An in-depth Vt analysis conducted for eight relevant brain structures confirmed the statistically significant differences between the levetiracetam group and the other groups ( p < 0.001) and highlighted the superior and the inferior colliculi along with the cortex as regions also displaying statistically significant differences between the vehicle and SV2B groups ( p < 0.05). These results emphasize the in vivo specificity of [ 18 F]UCB-H for SV2A against SV2B and SV2C, confirming that [ 18 F]UCB-H is a suitable radiotracer for in vivo imaging of the SV2A proteins with PET.
Databáze: MEDLINE
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