Everix Liesbeth, Elvas Filipe, Miranda Menchaca Alan, Khetarpal Vinod, Liu Longbin, Bard Jonathan, Staelens Steven, Bertoglio Daniele
Molecular Imaging Center Antwerp (MICA), University of Antwerp, Wilrijk, Belgium.
Molecular Imaging and Radiology (MIRA), Wilrijk, Belgium.
J Cereb Blood Flow Metab. 2025 May;45(5):920-931. doi: 10.1177/0271678X241304923. Epub 2024 Dec 4.
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.
突触囊泡蛋白2A（SV2A）在突触前终末广泛表达，在其中作为神经传递调节蛋白发挥作用。据报道，在健康衰老过程以及多种神经退行性疾病中会出现突触病变。SV2A的正电子发射断层扫描（PET）成像可用于评估突触密度。PET配体[C]UCB - J对SV2A具有高结合亲和力和选择性，但由于碳同位素，其物理半衰期较短。在此，我们报告了其氟标记等效物[F]UCB - J在C57BL / 6J小鼠中的特异性、重现性和稳定性的表征及验证。血浆分析显示至少有一种极性放射性代谢物。使用基于群体的代谢物校正图像衍生输入函数（IDIF）进行动力学建模。[F]UCB - J显示出相对较快的动力学以及基于IDIF的分布容积（）的可靠测量值。通过左乙拉西坦阻断试验（50至200mg / kg）证实了[F]UCB - J对SV2A的特异性。通过重测分析确定了的重现性，显示出显著相关性（r = 0.773，< 0.0001）。时间稳定性分析表明60分钟的扫描持续时间足以获得可靠的。总之，[F]UCB - J是一种在小鼠中具有最佳动力学的选择性SV2A配体。有必要进一步研究[F]UCB - J在突触病变中的（预）临床适用性。
