Direct Comparison of the Tau PET Tracers ¹⁸F-Flortaucipir and ¹⁸F-MK-6240 in Human Subjects

Tau PET tracers exhibit varying levels of specific signal and distinct off-target binding patterns that are more diverse than amyloid PET tracers. This study compared 2 frequently used tau PET tracers, ¹⁸F-flortaucipir and ¹⁸F-MK-6240, in the same subjects. Methods:¹⁸F-flortaucipir and ¹⁸F-MK-6240 scans were collected within 2 mo in 15 elderly subjects varying in clinical diagnosis and cognition. FreeSurfer, version 5.3, was applied to 3-T MR images to segment Braak pathologic regions (I-VI) for PET analyses. Off-target binding was assessed in the choroid plexus, meninges, and striatum. SUV ratio (SUVR) outcomes were determined over 80-100 min (¹⁸F-flortaucipir) or 70-90 min (¹⁸F-MK-6240) normalized to cerebellar gray matter. Masked visual interpretation of images was performed by 5 raters for both the medial temporal lobe and the neocortex, and an overall (majority) rating was determined. Results: Overall visual ratings showed complete concordance between radiotracers for both the medial temporal lobe and the neocortex. SUVR outcomes were highly correlated (r² > 0.92; P ≪ 0.001) for all Braak regions except Braak II. The dynamic range of SUVRs in target regions was approximately 2-fold higher for ¹⁸F-MK-6240 than for ¹⁸F-flortaucipir. Cerebellar SUVs were similar for ¹⁸F-MK-6240 and ¹⁸F-flortaucipir, suggesting that differences in SUVRs are driven by specific signals. Apparent off-target binding was observed often in the striatum and choroid plexus with ¹⁸F-flortaucipir and most often in the meninges with ¹⁸F-MK-6240. Conclusion: Both ¹⁸F-MK-6240 and ¹⁸F-flortaucipir are capable of quantifying signal in a common set of brain regions that develop tau pathology in Alzheimer disease; these tracers perform equally well in visual interpretations. Each also shows distinct patterns of apparent off-target binding. ¹⁸F-MK-6240 showed a greater dynamic range in SUVR estimates, which may be an advantage in detecting early tau pathology or in performing longitudinal studies to detect small interval changes.