Cerebral Oxidative Stress in Early Alzheimer’s Disease Evaluated by (64)Cu-ATSM PET/MRI: A Preliminary Study

Oxidative stress imaging using diacetyl-bis (N(4)-methylthiosemicarbazone) (Cu-ATSM) was applied to the evaluation of patients with early Alzheimer’s disease (eAD). Ten eAD patients (72 ± 9 years) and 10 age-matched healthy controls (HCs) (73 ± 9 years) participated in this study. They underwent dynamic PET/MRI using (11)C-PiB and (64)Cu-ATSM with multiple MRI sequences. To evaluate cerebral oxidative stress, three parameters of (64)Cu-ATSM PET were compared: standardized uptake value (SUV), tracer influx rate (K(in)), and a rate constant k(3). The input functions were estimated by the image-derived input function method. The relative differences were analyzed by statistical parametric mapping (SPM) using SUV and K(in) images. All eAD patients had positive and HC subjects had negative PiB accumulation, and MMSE scores were significantly different between them. The (64)Cu-ATSM accumulation tended to be higher in eAD than in HCs for both SUV and K(in). When comparing absolute values, eAD patients had a greater K(in) in the posterior cingulate cortex and a greater k(3) in the hippocampus compared with lobar cortical values of HCs. In SPM analysis, eAD had an increased left operculum and decreased bilateral hippocampus and anterior cingulate cortex compared to HCs. (64)Cu-ATSM PET/MRI and tracer kinetic analysis elucidated cerebral oxidative stress in the eAD patients, particularly in the cingulate cortex and hippocampus.