Biomarkers

Abstract

Background: Differences between on- and off-target retention characteristics between [¹⁸F]MK6240 and [¹⁸F]Flortaucipir (FTP) complicate the harmonization across tracers. Our objective here was to separate the impact of the reference region by evaluating correlations between [¹⁸F]MK6240 (MK) and [¹⁸F]FTP standard uptake values (SUVs).

Method: Participants (Figure 1, n=90) received an amyloid-β (Aβ) PET scan ([¹¹C]PIB or [¹⁸F]NAV4694) and two tau-PET scans: [¹⁸F]MK (90-110 minutes post-injection) and [¹⁸F]FTP (80-100 minutes post-injection). For all PET scans, the individual frames were realigned, averaged, and co-registered to a Freesurfer 7.1-segmented T1-MPRAGE. SUVs were calculated in the reference region (inferior cerebellar gray), on-target regions (entorhinal cortex, hippocampus, Braak III, Braak IV, Braak V, Braak VI) and off-target regions (caudate, pallidum, putamen, thalamus, cerebellar white matter, choroid plexus, meninges, eroded white matter). We examined correlations between [¹⁸F]MK and [¹⁸F]FTP SUV values as a function of Aβ status, as well as their associations with age.

Result: All correlations (Figure 2) were significant at p<0.001. The interaction with Aβ status was significant for hippocampus, BraakIII-V and the metatemporal region. In Aβ+ participants, [¹⁸F]FTP and [¹⁸F]MK6240 have similar SUVs in on-target regions with a slope close to 1 except for in hippocampus and Braak VI. However, [¹⁸F]FTP SUVs, on average, were greater than [¹⁸F]MK SUVs in Aβ+ and Aβ- subjects in the reference region and all off-target regions except for meninges, and in Aβ- subjects in the on-target regions. Age correlated with [¹⁸F]FTP SUVs in Aβ- subjects in all regions (except the reference region, Braak VI and meninges) and [¹⁸F]MK SUVs in putamen and pallidum, but this correlation was only significant (p<0.01) when young and old subjects were included.

Conclusion: Despite [¹⁸F]MK's higher affinity for tau and SUVR dynamic range being twice that of [¹⁸F]FTP, the SUVs in on-target regions are similar. The higher [¹⁸F]FTP signal in the reference region appears to be the contributing factor to the lower dynamic range. The higher [¹⁸F]FTP signal in on-target regions for Aβ- subjects may reflect the presence of off-target signals in these subjects. Taking off-target signals into account should improve correlations between the two tracers, especially when measuring the earliest deposition of tau.