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 11CUCB-J, 18FUCB-J, and 18FSynVesT-1. To compare the in vivo performance of the PET radioligands 18FUCB-J and 18FSynVesT-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 k2 for 18FSynVesT-1 compared to 18FUCB-J. VT(IDIF) (Logan) quantification found significantly higher values for 18FSynVesT-1 compared to 18FUCB-J regardless of genotype (e.g. striatum WT: 22.4 ± 2.7 vs 18.6 ± 1.8 mL/cm3). Regional analyses comparing the average VT(IDIF) between genotypes showed no significant differences; however, voxel-based VT(IDIF) analyses revealed significant SV2A alterations in several subregions of the brain for both radioligands. Overall, 18FSynVesT-1 and 18FUCB-J showed agreement across analyses, demonstrating the equal applicability of both radioligands for SV2A PET imaging.
Everix et al. (Sun,) studied this question.