Preclinical Validation and Kinetic Modelling of the SV2A PET Ligand [F]UCB-J in Mice

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2024 Dec 4

PMID 39628318

Authors

Liesbeth Everix

Filipe Elvas

Alan Miranda Menchaca

Vinod Khetarpal

Longbin Liu

Jonathan Bard

Steven Staelens

Daniele Bertoglio

Affiliations

Soon will be listed here.

Abstract

Synaptic vesicle protein 2A (SV2A) is ubiquitously expressed in presynaptic terminals where it functions as a neurotransmission regulator protein. Synaptopathy has been reported during healthy ageing and in a variety of neurodegenerative diseases. Positron emission tomography (PET) imaging of SV2A can be used to evaluate synaptic density. The PET ligand [C]UCB-J has high binding affinity and selectivity for SV2A but has a short physical half-life due to the C isotope. Here we report the characterization and validation of its F-labeled equivalent, [F]UCB-J, in terms of specificity, reproducibility and stability in C57BL/6J mice. Plasma analysis revealed at least one polar radiometabolite. Kinetic modelling was performed using a population-based metabolite corrected image-derived input function (IDIF). [F]UCB-J showed relatively fast kinetics and a reliable measure of the IDIF-based volume of distribution (). [F]UCB-J specificity for SV2A was confirmed through a levetiracetam blocking assay (50 to 200 mg/kg). Reproducibility of the was determined through test-retest analysis, revealing significant correlation (r = 0.773, < 0.0001). Time-stability analyses indicate a scan duration of 60 min to be sufficient to obtain a reliable . In conclusion, [F]UCB-J is a selective SV2A ligand with optimal kinetics in mice. Further investigation is warranted for (pre)clinical applicability of [F]UCB-J in synaptopathies.

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