Pharmacokinetic Characterization of [18F]UCB-H PET Radiopharmaceutical in the Rat Brain

TY - JOUR

T1 - Pharmacokinetic Characterization of [18F]UCB-H PET Radiopharmaceutical in the Rat Brain

AU - Becker, Guillaume

AU - Warnier, Corentin

AU - Serrano, Maria Elisa

AU - Bahri, Mohamed Ali

AU - Mercier, Joël

AU - Lemaire, Christian

AU - Salmon, Eric

AU - Luxen, André

AU - Plenevaux, Alain

PY - 2017/8/7

Y1 - 2017/8/7

N2 - 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, [18F]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 [18F]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 [18F]UCB-H and confirmed the negligible amount of radiometabolites in the rat brain. Hence, the in vivo quantification of SV2A using [18F]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.

AB - 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, [18F]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 [18F]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 [18F]UCB-H and confirmed the negligible amount of radiometabolites in the rat brain. Hence, the in vivo quantification of SV2A using [18F]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.

KW - Animals

KW - Brain/metabolism

KW - Fluorine Radioisotopes/chemistry

KW - Male

KW - Positron-Emission Tomography

KW - Pyrrolidinones/chemistry

KW - Radiopharmaceuticals/pharmacokinetics

KW - Rats

KW - Reproducibility of Results

U2 - 10.1021/acs.molpharmaceut.7b00235

DO - 10.1021/acs.molpharmaceut.7b00235

M3 - Article

C2 - 28651055

SN - 1543-8384

VL - 14

SP - 2719

EP - 2725

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

IS - 8

ER -