Assessing Synaptic Density in Behavioral Variant Frontotemporal Dementia: A Head-to-Head Comparison of 18F-SynVesT-1 and 18F-FDG PET
Salih Cayir1, Yanghong Yang4, Waleed Ibrahim1, Mika Naganawa1, Jean-Dominique Gallezot1, Takuya Toyonaga1, Nabeel Nabulsi1, Henry huang1, Richard Carson1, Christopher Vandyck2, Adam Mecca2, Arman Fesharaki-Zadeh3, David Matuskey1
1Radiology and Biomedical Imaging, 2Alzheimer Disease Research Unit, 3Neurology, Yale University, 4Neurology, SUNY Downstate Health Sciences University
Objective:
To assess the distribution patterns and group differences in behavioral variant frontotemporal dementia (bvFTD) patients and healthy controls (HC) using 18F-SynVestT-1 binding, and compare these results with 18F-fluorodeoxyglucose (18F-FDG) in brain regions associated with bvFTD pathology.
Background:
Synaptic loss is a key pathological process in bvFTD that may drive disease progression. Here, we use in vivo positron emission tomography (PET) imaging with 18F-SynVest-1, a newly developed PET imaging tool from our group that provides quantitative data of synaptic vesicle glycoprotein 2A (SV2A), a marker of synaptic density, to compare with 18F-FDG.
Design/Methods:
Ten individuals (mean age (SD): 67(10); seven males) with bvFTD and three demographically matched healthy controls (HC; 69(2); three females) participated in both 18F-SynVesT-1 and 18F-FDG scans.Additionally, five controls (58(3); four males) participated in 18F-SynVestT-1 scans only, and thirteen controls (HC; 74 (9); seven males) participated in 18F-FDG scans only for comparison purposes. Binding potential (BPND) and the influx rate constant (Ki) were the primary outcome measures for 18F-SynVesT-1 and 18F-FDG, respectively. The regions of interest were defined using FreeSurfer on MRIs and then applied to PET images. T-tests were used to evaluate between-group differences.Pearson correlations were calculated to investigate associations between synaptic density, glucose metabolism, and bvFTD disease severity.
Results:
We observed lower synaptic density and glucose metabolism in bvFTD patients compared to HC in the frontal lobe (-30.1%, p<0.01 for 18F-SynVesT-1;-25.9%,p=0.01 for 18F-FDG), insula (-26%, p=0.01; -17.1%,p=0.04), temporal lobe (-26.6%,p=0.01;-18.9%,p=0.03), anterior cingulate cortex (-35.1%, p<0.01;-26.6%,p=0.01), and hippocampus (-30.6%, p<0.01;-18.5%,p=0.05). Higher synaptic density in the frontal cortex was significantly associated with better performance on the Frontal Assessment Battery (r=0.83,p=0.01) and the MoCA (r=0.67,p=0.03). Glucose metabolism was not significantly correlated with cognitive measures in any brain region.
Conclusions:
These preliminary results suggest that synaptic abnormalities detected by SV2A imaging with 18F-SynVesT-1 PET may outperform the clinical marker 18F-FDG in patients with bvFTD.
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