Abstract
ObjectivesIn recent years several [18F]-labelled amyloid PET tracers have been developed and have obtained clinical approval. There is accumulating evidence that early (post injection) acquisitions with these tracers are equally informative as conventional blood flow and metabolism studies for diagnosis of Alzheimer's disease, but there have been few side-by-side studies. Therefore, we investigated the performance of early acquisitions of [18F]-florbetaben (FBB) PET compared to [18F]-fluorodeoxyglucose (FDG) PET in a clinical setting.MethodsAll subjects were recruited with clinical suspicion of dementia due to neurodegenerative disease. FDG PET was undertaken by conventional methods, and amyloid PET was performed with FBB, with early recordings for the initial 10 min (early-phase FBB), and late recordings at 90–110 min p.i. (late-phase FBB). Regional SUVR with cerebellar and global mean normalization were calculated for early-phase FBB and FDG PET. Pearson correlation coefficients between FDG and early-phase FBB were calculated for predefined cortical brain regions. Furthermore, a visual interpretation of disease pattern using 3-dimensional stereotactic surface projections (3D-SSP) was performed, with assessment of intra-reader agreement.ResultsAmong a total of 33 patients (mean age 67.5 ± 11.0 years) included in the study, 18 were visually rated amyloid-positive, and 15 amyloid-negative based on late-phase FBB scans. Correlation coefficients for early-phase FBB vs. FDG scans displayed excellent agreement in all target brain regions for global mean normalization. Cerebellar normalization gave strong, but significantly lower correlations. 3D representations of early-phase FBB visually resembled the corresponding FDG PET images, irrespective of the amyloid-status of the late FBB scans.ConclusionsEarly-phase FBB acquisitions correlate on a relative quantitative and visual level with FDG PET scans, irrespective of the amyloid plaque density assessed in late FBB imaging. Thus, early-phase FBB uptake depicts a metabolism-like image, suggesting it as a valid surrogate marker for synaptic dysfunction, which could ultimately circumvent the need for additional FDG PET investigation in diagnosis of dementia.
Highlights
IntroductionAmyloid plaques play a role in early pathogenesis of Alzheimer's disease (AD), and may even be present 10– 15 years prior to onset of discernible cognitive decline, before developing to a stable level observed at the clinical stages of AD (Kadir et al, 2012)
The extensive amyloid accumulation during the pre-clinical course may disfavor the use of FBB and related Positron emission tomography (PET) tracers to determine the extent of neurodegeneration or to monitor disease progression in clinical stages of Alzheimer's disease (AD) (Furst et al, 2012)
The group consisted of 11 subjects with a clinical diagnosis of mild cognitive impairment (MCI) and 22 demented subjects with different clinical presentations: 11 of these cases had a most likely diagnosis of AD, four were likely suffering from frontotemporal lobar degeneration (FTLD), single cases of primary progressive aphasia or corticobasal degeneration and five cases with ambiguous clinical and biomarker presentation
Summary
Amyloid plaques play a role in early pathogenesis of AD, and may even be present 10– 15 years prior to onset of discernible cognitive decline, before developing to a stable level observed at the clinical stages of AD (Kadir et al, 2012). The extensive amyloid accumulation during the pre-clinical course may disfavor the use of FBB and related PET tracers to determine the extent of neurodegeneration or to monitor disease progression in clinical stages of AD (Furst et al, 2012). Findings with more conventional [18F]fluorodeoxyglucose (FDG) PET for measuring cerebral glucose metabolism, or perfusion SPECT scans, are a much more sensitive indicator for disease stage, and can provide information about synaptic dysfunction and the degree of neurodegeneration (Herholz, 2011; Shokouhi et al, 2013)
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