Evaluation of increased oxidative stress in the brain of patients with early Alzheimer’s disease by 64Cu-ATSM PET/MRI

We aimed to compare brain oxidative stress (OS) levels between patients with early Alzheimer's disease (eAD) and age-matched cognitively normal (CN) individuals using ⁶⁴Cu-diacetyl-bis(N4-methylthiosemicarbazone) (⁶⁴Cu-ATSM) PET/MRI. Thirty-seven patients with eAD (71.8±8.0 years) and 14 CN (71.1±7.7 years) were included in this study. They underwent PET/MRI using Pittsburg compound-B (¹¹C-PiB) and ⁶⁴Cu-ATSM on separate days. Each standardized uptake value (SUV) image was converted to an SUV ratio (SUVR) image using the individual cerebellar SUV as a reference. ¹¹C-PiB centiloid (CL) scale was calculated from a whole-brain image and compared with other biomarkers. The Patlak plot method was used to calculate the influx rate constant (K_in) image of ⁶⁴Cu-ATSM to evaluate the global and regional brain OS levels. Hippocampal volume was also evaluated using three-dimensional T1-weighted MRI. All eAD patients showed positive PiB accumulation, whereas all CN individuals showed negative accumulation. Significant group differences were found in the Mini-Mental State Examination score, Clinical Dementia Rating (CDR) score, Alzheimer's Disease Assessment Scale (ADAS), hippocampal volume, and PiB-CL. ⁶⁴Cu-ATSM K_in images showed significant positive correlations with PiB-CL in the hippocampus and posterior cingulate cortex of eAD patients. ⁶⁴Cu-ATSM SUVR in the hippocampus was negatively correlated with hippocampal volume, CDR score. A significant positive correlation between ⁶⁴Cu-ATSM K_in and PiB-CL was observed in the regions responsible for eAD, suggesting that increased OS levels in the brain are associated with the progression of amyloid deposition. These findings indicate ⁶⁴Cu-ATSM PET is a useful and promising OS evaluation tool.