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Comparative Study
. 2018;62(4):1595-1607.
doi: 10.3233/JAD-170582.

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

Lisa Flem Kalheim  1   2 , Tormod Fladby  1   2 , Christopher Coello  3 , Atle Bjørnerud  4 , Per Selnes  1   2
Affiliations
Comparative Study

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

Lisa Flem Kalheim et al. J Alzheimers Dis. 2018.

Abstract

Flutemetamol (18F-Flut) is an [18F]-labelled amyloid PET tracer with increasing availability. The main objectives of this study were to investigate 1) cerebrospinal fluid (CSF) Aβ 1-42 (Aβ42) concentrations associated with regional 18F-Flut uptake, 2) associations between cortical 18F-Flut and [18F]-fludeoxyglucose (18F-FDG)-PET, and 3) the potential use of 18F-Flut in WM pathology. Cognitively impaired, nondemented subjects were recruited (n = 44). CSF was drawn, and 18F-Flut-PET, 18F-FDG-PET, and MRI performed. Our main findings were: 1) Different Alzheimer's disease predilection areas showed increased 18F-Flut retention at different CSF Aβ42 concentrations (posterior regions were involved at higher concentrations). 2) There were strong negative correlations between regional cortical 18F-Flut and 18F-FDG uptake. 3) Increased 18F-Flut uptake were observed in multiple subcortical regions in amyloid positive subjects, including investigated reference regions. However, WM hyperintensity 18F-Flut standardized uptake value ratios (SUVr) were not significantly different, thus we cannot definitely conclude that the higher uptake in 18F-Flut(+) is due to amyloid deposition. In conclusion, our findings support clinical use of CSF Aβ42, putatively relate decreasing CSF Aβ42 concentrations to a sequence of regional amyloid deposition, and associate amyloid pathology to cortical hypometabolism. However, we cannot conclude that 18F-Flut-PET is a suitable marker for WM pathology due to high aberrant WM uptake.

Keywords: Alzheimer’s disease; cerebrospinal fluid; imaging; positron emission tomography; white matter disease.

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Figures

Fig.1
Fig.1
Inclusions and exclusions in the cohort. Two subjects of <55 years of age were excluded to limit between-group age differences. PET, positron emission tomography; WMH, white matter hyperintensities; 18F-Flut, 18F-Flutemetamol.
Fig.2
Fig.2
Associations between regional 18F-Flutemetamol SUVr and CSF Aβ42. Based on the visual interpretation by a trained reader, the subjects are marked as 18F-Flut(+) (green dots) or 18F-Flut(–) (blue dots). Using an SUVr cut-off of 1.46 yields different CSF Aβ42 cut-offs for each pre-selected region. SUVr, standardized uptake value ratios; CSF, cerebrospinal fluid; Aβ42, amyloid-β 1-42.
Fig.3
Fig.3
Receiver operating characteristic (ROC) curves for the accuracy of each CSF Aβ42 cut-off to predict regional 18F-Flutemetamol abnormality.
See this image and copyright information in PMC

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