Arman Fesharaki‐Zadeh, Salih Cayir, Waleed Ibrahim, Yanghong Yang, Jean‐Dominique Gallezot, Mika Naganawa, Yanjun Wu, Takuya Toyonaga, Faranak Ebrahimian Sadabad, Ryan S O'Dell, Brian Pittman, Nabeel Nabulsi, Stephen Strittmatter, Richard E. Carson, Yiyun Huang, Christopher H. van Dyck, Adam P. Mecca, David Matuskey
Abstract INTRODUCTION Synapse loss, a key feature of behavioral variant frontotemporal dementia (bvFTD), can now be visualized in vivo using positron emission tomography (PET) that targets synaptic vesicle glycoprotein 2A (SV2A). Comparing this new imaging method with the clinical standard of glucose metabolism using 1 8 F‐fluorodeocyglucose ( 1 8 F‐FDG) PET might improve diagnostic accuracy and disease monitoring in bvFTD. METHODS We measured synaptic vesicle glycoprotein 2A (SV2A) binding using 1 8 F‐SynVesT‐1 PET and glucose metabolism with 1 8 F‐FDG PET in 10 patients with bvFTD and 10 age‐matched healthy controls. RESULTS SV2A binding was significantly lower in the frontal and temporal cortices, anterior cingulate, and insula in bvFTD patients, with more widespread and pronounced differences than those observed with 1 8 F‐FDG PET. SV2A binding in the frontal cortex and insula significantly correlated with the Frontal Assessment Battery scores. DISCUSSION Our findings suggest that, in bvFTD, the degree of lower synaptic density, as measured by SV2A PET, is larger than the degree of hypometabolism as measured by 1 8 F‐FDG PET. SV2A imaging demonstrates considerable promise as a new in vivo biomarker for bvFTD.