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Abstract Purpose 18 Fflortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer’s disease (AD). However, “off-target” binding interferes with the quantification of 18 Fflortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare 18 Fflortaucipir with the novel tau tracer 18 FRO948 head-to-head in vivo. Methods We included 18 participants with AD, three with amyloid-β-positive amnestic mild cognitive impairment, and four healthy controls. All underwent 18 Fflortaucipir (80–100 min) and 18 FRO948 (70–90) PET scans within approximately 1 month. Four study participants underwent 0–100-min dynamic scanning. Standardized uptake value ratios (SUVRs) were created using an inferior cerebellar reference region. Results Neocortical tracer retention was highly comparable using both SUVR and distribution volume ratio-1 values obtained from dynamic scans. However, 18 FRO948 retention was significantly higher in the entorhinal cortex and lower in the basal ganglia, thalamus, and choroid plexus compared with 18 Fflortaucipir. Increased off-target binding was observed with age for both tracers. Several cases exhibited strong 18 FRO948 retention in the skull/meninges. This extra-cerebral signal, however, did not affect diagnostic accuracy and remained relatively unchanged when re-examining a subsample after 1 year. Kinetic modeling showed an increase in 18 Fflortaucipir SUVR over the scanning interval, compared with a plateau for 18 FRO948. Conclusion 18 FRO948 and 18 Fflortaucipir bound comparably in neocortical regions, but 18 FRO948 showed higher retention in the medial temporal lobe and lower intracerebral “off-target” binding. Time-dependent bias of SUVR estimates may prove less of a factor with 18 FRO948, compared with previous tau ligands.
Smith et al. (Mon,) studied this question.