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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Pharmacokinetic Characterization of [ 18 F]UCB-H PET Radiopharmaceutical in the Rat Brain.
Molecular Pharmaceutics 2017 August 8
The synaptic vesicle glycoprotein 2A (SV2A), a protein essential to the proper nervous system function, is found in presynaptic vesicles. Thus, SV2A targeting, using dedicated radiotracers combined with positron emission tomography (PET), allows the assessment of synaptic density in the living brain. The first-in-class fluorinated SV2A specific radioligand, [18 F]UCB-H, is now available at high activity through an efficient radiosynthesis compliant with current good manufacturing practices (cGMP). We report here a noninvasive method to quantify [18 F]UCB-H binding in rat brain with microPET. Validation study in rats confirmed the need of high enantiomeric purity to target SV2A in vivo. We demonstrated the reliability of a population-based input function to quantify SV2A in preclinical microPET setting. Finally, we investigated the in vivo metabolism of [18 F]UCB-H and confirmed the negligible amount of radiometabolites in the rat brain. Hence, the in vivo quantification of SV2A using [18 F]UCB-H microPET seems a promising tool for the assessment of the synaptic density in the rat brain, and opens the way for longitudinal follow-up in neurodegenerative disease rodent models.
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