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• W2897325326 abstract "Determining early tau accumulation is important for studying aging and AD, and is only as accurate as the signal to noise ratio of the tracer. Along with tau, [18F]-AV-1451 has been reported to bind to neuromelanin, MAO, iron, lepto-meningeal melanocytes, and microhemorrhages. [18F]-AV-1451 successfully differentiates healthy controls (HCs) from ADs, however we wanted to explore off-target binding and the variability seen in HCs expected to have no tau accumulation (Figure 1). Variability in [18F]-AV-1451 signal in amyloid negative subjects (group 1). Subject groups are described in Table 1. In groups 1-2, T1-weighted MRIs were segmented using Freesurfer, SUVRs 80-100 min ([18F]-AV-1451) and 50-70 min ([11C]-PIB) post-injection were calculated with and without partial volume correction (PVC; Rousset method, same for both tracers); reference region was inferior cerebellar gray. In amyloid negative HCs (group 1), linear models were used on PVC data to explore relationships between cortical uptake, age, and non-specific binding ROIs (nsROIS: thalamus, putamen, pallidum, caudate, and white matter). Mean [18F]-AV-1451 ROI values from group 2 were compared to the iron-load distribution in group 3 (VanBergen et al, 2018). Figure 2 shows r2 for PVC and non-PVC nsROIs. There are two groups of nsROIs, one that is age-related (caudate, putamen, pallidum), and the other composed of white matter and thalamus. We compared non-PVC and PVC correlations between white matter and whole cortex for [11C]-PIB and [18F]-AV-1451 SUVRs. Figure 3 shows white matter correlation with cortex was removed after PVC in [11C]-PIB but not in [18F]-AV-1451, proving the [18F]-AV-1451 correlation stems from non-specific binding in both gray and white matter, not partial volume effects. Figure 4 shows the r2 between cortical regions and non-specific binding regions in [18F]-AV-1451. 67.4% of the variability in whole cortex can be explained by non-specific binding in the putamen and thalamus. Figure 5 shows the mean distribution in older adults of iron regionally co-varies with [18F]-AV-1451. Correlations (r2) between age and non-specific binding ROIs in amyloid negative healthy controls (group 1). Correlation between white matter and whole cortex in [11C]-PIB and [18F]-AV-1451. r2 (adjusted r2 for Putamen + Thalamus) Cortical ROIs and Age / Non-Specific Binding ROIs (all PVC). Iron load and [18F]-AV-1451 distribution in older healthy controls. There are two types of [18F]-AV-1451 non-specific binding in the cortex in HCs. One related to age that best correlates with putamen (possibly explained by iron), the other related to white matter and thalamus. This should be considered when studying the earliest accumulation of tau." @default.
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• W2897325326 date "2018-07-01" @default.
• W2897325326 modified "2023-10-16" @default.
• W2897325326 title "IC‐02‐03: EXPLAINING [ ¹⁸ F]‐AV‐1451 VARIABILITY IN HEALTHY CONTROLS ACROSS THE LIFESPAN" @default.
• W2897325326 doi "https://doi.org/10.1016/j.jalz.2018.06.2046" @default.
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