Direct Comparison of the Tau PET Tracers18F-Flortaucipir and18F-MK-6240 in Human Subjects

Authors: Alexandra Gogola, Davneet Minhas, Victor L. Villemagne, Ann D. Cohen, James M. Mountz, Tharick A. Pascoal, Charles M. Laymon, N. Scott Mason, Miloš D. Ikonomović, Chester A. Mathis, Beth E. Snitz, Oscar L. López, William E. Klunk, Brian J. Lopresti - Journal of Nuclear Medicine 2021 cited by 94

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, 18 F-flortaucipir and 18 F-MK-6240, in the same subjects. Methods: 18 F-flortaucipir and 18 F-MK-6240 scans were collected within 2 mo in 15 elderly subjects varying in clinical diagnosis and cognition. Free-Surfer, 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 ( 18 F-flortaucipir) or 70-90 min ( 18 F-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 (r 2 . 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 18 F-MK-6240 than for 18 F-flortaucipir. Cerebellar SUVs were similar for 18 F-MK-6240 and 18 F-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 18 F-flortaucipir and most often in the meninges with 18 F-MK-6240. Conclusion: Both 18 F-MK-6240 and 18 F-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. 18 F-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.