TY - JOUR T1 - In vivo imaging of synaptic loss in spinocerebellar ataxia type 3 with [18F]SDM-8 positron emission tomography JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 262 LP - 262 VL - 61 IS - supplement 1 AU - Guang Liao AU - Ming Zhou AU - YongXiang Tang AU - Jie Yu AU - Shuo Hu Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/262.abstract N2 - 262Objectives: Spinocerebellar ataxia type 3(SCA3) is the most common inherited spinocerebellar ataxia and one of many polyglutamine neurodegenerative diseases, caused by trinucleotide (CAG) repeat expansion in exon 10 of the ATXN3 gene on chromosome14 (p32). Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms and progression of disease associated with SCA3. The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect estimate of synaptic density. The aim of our study is to use positron emission tomography (PET) with the SV2A radioligand [18F]SDM-8 to examine synaptic of SCA3 with different clinical stages. Methods: The study was approved by the institutional review board. We recruited a total of 28 SCA3 patients (16 females) and 3 healthy controls (1 female). All patients diagnosed by genetic testing and stratified to preclinical stage group (PSG) and clinical stage group (CSG) based on severity of clinical symptoms using a Scale for the Assessment and Rating of Ataxia (SARA) cut-off score of 4. Individuals with SARA scores <4 were classified into PSG (n=6) and individuals with SARA scores ≥4 were classified as the CSG (n=22). All participants underwent [18F]SDM-8 PET imaging and a semi-quantitative analysis with standardized uptake value ratio (SUVR) was developed. Regions-of-interest (ROIs) were delineated for standardized uptake value (SUVmax and SUVmean) measurement respectively in the 10 regions including vermis, cerebellar cortex, brainstem, thalamus, cauda nucleus, striatum, parietal cortex, frontal cortex, temporal cortex and hippocampus. SUVR was calculated with the white matter in the center of semi-oval as the reference region. A Mann-Whitney U test was run to determine if there were differences in SUVR between SCA3 patients and HC by SPSS (IBM SPSS Statistics, Version 21.0). Statistical significance is defined as p<0.05. Results: There were no significant differences between the SCA3 patients and the HC with age, while the CSG patients (41.2±8.1, y) were older than PSG patients (34.7±4.5, y) with a statistical difference (p<0.05) . The SUVRmax and SUVmean in SCA3 patients were lower than those in HC in the most regions except the hippocampus, but only the SUVRs (both SUVRmax and SUVmean) in vermis, cerebellar cortex, brainstem, frontal cortex and cauda nucleus have significant differences (p<0.05). The similar trend was showed between the PSG and the CSG, but the differences of SUVRs were no significant between the two groups in both 10 regions. Conclusions: The study demonstrated that the new SV2A tracer agent [18F]SDM-8 PET imaging allows to image in vivo synaptic changes in SCA3 patients, showed synaptic density decreased in the vermis, cerebellar cortex, brainstem, frontal cortex and cauda nucleus of SCA3 patients when compared to the health controls. It will be a new reliable tool to assess critical neuropathological changes during the lifetime of SCA3 patients and improve a better clinical decision management with larger sample size and more accurate quantitative analysis. Acknowledgements: This study was supported by the National Natural Science Foundation of China, Grant No. 81801740. ER -