[(18)F]-Flutemetamol Uptake in Cortex and White Matter: Comparison with Cerebrospinal Fluid Biomarkers and [(18)F]-Fludeoxyglucose

Flutemetamol ((18)F-Flut) is an [(18)F]-labelled amyloid PET tracer with increasing availability. The main objectives of this study were to investigate 1) cerebrospinal fluid (CSF) Aβ 1-42 (Aβ(42)) concentrations associated with regional (18)F-Flut uptake, 2) associations between cortical (18)F-Flut and [(18)F]-fludeoxyglucose ((18)F-FDG)-PET, and 3) the potential use of (18)F-Flut in WM pathology. Cognitively impaired, nondemented subjects were recruited (n = 44). CSF was drawn, and (18)F-Flut-PET, (18)F-FDG-PET, and MRI performed. Our main findings were: 1) Different Alzheimer’s disease predilection areas showed increased (18)F-Flut retention at different CSF Aβ(42) concentrations (posterior regions were involved at higher concentrations). 2) There were strong negative correlations between regional cortical (18)F-Flut and (18)F-FDG uptake. 3) Increased (18)F-Flut uptake were observed in multiple subcortical regions in amyloid positive subjects, including investigated reference regions. However, WM hyperintensity (18)F-Flut standardized uptake value ratios (SUVr) were not significantly different, thus we cannot definitely conclude that the higher uptake in (18)F-Flut(+) is due to amyloid deposition. In conclusion, our findings support clinical use of CSF Aβ(42), putatively relate decreasing CSF Aβ(42) concentrations to a sequence of regional amyloid deposition, and associate amyloid pathology to cortical hypometabolism. However, we cannot conclude that (18)F-Flut-PET is a suitable marker for WM pathology due to high aberrant WM uptake.