Evaluation of regional distribution of the PET tau tracer 18F-AV1451 (also known as 18F-T807) using SUVr analysis and voxel wise parametric mapping

Objectives F18-AV1451 is a PET tracer in development for the assessment of tau neurofibrillary tangles. We investigated regional involvement in different diagnostic groups using voxel-wise statistical parametric maps and, for comparison, a standard regional SUVr analysis.

Methods 18F-AV-1451 images were acquired 80-100 min post injection in 154 subjects [14 young and 34 older healthy controls, 72 MCI and 34 AD]. T1 weighted MRI, and florbetapir amyloid PET scans were also obtained. SUVr values were calculated from AAL VOIs masked for gray matter in MNI atlas space. Data were grouped by amyloid status (Aβ+=SUVr>1.10) and clinical diagnosis. SPM was used to perform voxel-wise two-sample t-test analysis across diagnostic groups resulting in cluster T-value images. Finally, AAL and voxel-wise SUVr values from clinically diagnosed and amyloid-status groups were evaluated for correlation with cognitive scores (ADAS and MMSE).

Results Aβ+AD(N=22) vs. Aβ-AD(N=12) revealed significant differences (P<0.001) in temporal, parietal and superior prefrontal regions. Aβ+MCI(N=35) vs. Aβ-MCI(N=37), showed significant differences (P<0.001) in lateral tempo-parietal and medial temporal regions. Aβ+AD vs. Aβ+MCI showed fewer areas with significant differences compared to Aβ+AD vs. Aβ-AD, however, focal uptake was seen in lateral and medial parietal regions, more strongly on the right than left. In Aβ+ subjects with cognitive impairment, ADAS showed significant correlations in frontal, temporal and parietal regions (r = 0.23 to 0.52, P<0.05); MMSE was correlated in fewer regions than ADAS with the strongest correlations in temporal and parietal regions (r = -0.22 to -0.37, P<0.05).

Conclusions Both regional SUVr and voxel wise t-test analyses gave effective group differences in F18-AV1451 PET tau signal. Both ADAS and MMSE were seen to have significant correlations with tau signal in multiple brain regions, although the spatial distribution of the correlations were not identical across the two voxel-wise maps.