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Abstract

Deficits in the synaptic vesicle protein 2A (SV2A) have been reported in various neurodegenerative diseases including Alzheimer’s and Huntington’s disease (HD). SV2A levels can be investigated using positron emission tomography (PET) radioligands such as [¹¹C]UCB-J, [¹⁸F]UCB-J, and [¹⁸F]SynVesT-1. To compare the in vivo performance of the PET radioligands [¹⁸F]UCB-J and [¹⁸F]SynVesT-1 in terms of brain penetration, binding profile, and SV2A quantification, we here report a head-to-head study in a mouse model of HD. Dynamic µPET/CT scans (60 min) were acquired in 17-month-old heterozygous (HET, n = 20) zQ175DN and wild-type (WT, n = 19) mice. Brain time-activity curves and image-derived input function were extracted and kinetic modeling was performed using Logan and the two-tissue compartmental model (2TCM). Intra-animal comparison between both radioligands revealed significantly higher K₁ (p < 0.01) but equal k₂ for [¹⁸F]SynVesT-1 compared to [¹⁸F]UCB-J. V_T(IDIF) (Logan) quantification found significantly higher values for [¹⁸F]SynVesT-1 compared to [¹⁸F]UCB-J regardless of genotype (e.g. striatum WT: 22.4 ± 2.7 vs 18.6 ± 1.8 mL/cm³). Regional analyses comparing the average V_T(IDIF) between genotypes showed no significant differences; however, voxel-based V_T(IDIF) analyses revealed significant SV2A alterations in several subregions of the brain for both radioligands. Overall, [¹⁸F]SynVesT-1 and [¹⁸F]UCB-J showed agreement across analyses, demonstrating the equal applicability of both radioligands for SV2A PET imaging.

Keywords

Synaptic density SV2A positron emission tomography mouse kinetic modeling

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Comparing kinetic profiles of SV2A radiotracers [ 18 F]SynVesT-1 and [ 18 F]UCB-J using PET imaging in mice

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