The Pharmacokinetics of [18F]UCB-H Revisited in The Healthy Non-Human Primate Brain Article Swipe

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Sébastien Goutal , Martine Guillermier , Guillaume Becker , Mylène Gaudin , Yann Bramoullé , André Luxen , Christian Lemaire , Alain Plenevaux , Éric Salmon , Philippe Hantraye , Olivier Barret , Nadja Van Camp ·

YOU? · · 2020 · Open Access · · DOI: https://doi.org/10.21203/rs.3.rs-110220/v1

Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we aimed to characterize [18F]UCB-H in the non-human cynomolgus primate and to discuss the obtained results in the light of the current state of SV2A PET ligands.Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), even though a slow component led to instability for the estimation of k₃ and k₄, and hence the total volume of distribution. 2TCM with coupled fit K₁/k₂ across brain regions stabilized the quantification, and confirmed a lower non-displaceable binding potential, BP_ND (estimated by k₃/k₄), of [18F]UCB-H compared to the newest SV2A-ligands. However, the non-displaceable distribution volume (V_ND) and the influx parameter (K₁) is similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50 % displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

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Pharmacokinetics Non human primate Human brain Primate Medicine Neuroscience Psychology Pharmacology Biology Evolutionary biology

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Type: preprint
Language: en
Landing Page: https://doi.org/10.21203/rs.3.rs-110220/v1
PDF: https://www.researchsquare.com/article/rs-110220/v1.pdf?c=1605907375000
OA Status: gold
References: 25
Related Works: 10
OpenAlex ID: https://openalex.org/W4232406421

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DOI: https://doi.org/10.21203/rs.3.rs-110220/v1

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Title: The Pharmacokinetics of [18F]UCB-H Revisited in The Healthy Non-Human Primate Brain

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Language: en

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Publication year: 2020

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Publication date: 2020-11-20

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Authors: Sébastien Goutal, Martine Guillermier, Guillaume Becker, Mylène Gaudin, Yann Bramoullé, André Luxen, Christian Lemaire, Alain Plenevaux, Éric Salmon, Philippe Hantraye, Olivier Barret, Nadja Van Camp

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Landing page: https://doi.org/10.21203/rs.3.rs-110220/v1

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Concepts: Pharmacokinetics, Non human primate, Human brain, Primate, Medicine, Neuroscience, Psychology, Pharmacology, Biology, Evolutionary biology

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