IN VIVO COMPARISON OF TAU PET RADIOLIGANDS 18F-THK-5351 AND 18F-MK-6240

Abstract

The tau tracer 18F-THK-5351 has off-target binding to monoamine oxidase B (MAO-B). 18F-MK-6240 is an improved radioligand expected to be more specific for tau pathology. We sought to compare 18F-THK-5351 and 18F-MK-6240 binding in participants who had both PET scans. Seventeen subjects (age 68.1 ± 5.6 years) underwent neuropsychological testing, brain MRI, 18F-florbetaben PET to determine amyloid status, and 18F-THK-5351 PET (50-70 min acquisition). Ten subjects also underwent PET imaging with 18F-MK-6240 (80-100 min acquisition). For all radioligands, cerebellar gray matter was used to calculate standardized uptake value ratios (SUVR). While 18F-THK-5351 binding was greater in amyloid-positive patients than in amyloid-negative controls, amyloid-negative patients showed intermediate amounts of binding. In addition, 18F-THK-5351 binding correlated with 18F-MK-6240 binding in amyloid-positive subjects, but not in amyloid-negative subjects. In amyloid-positive subjects, 18F-THK-5351 binding was greater in putamen than in medial temporal cortex, whereas 18F-MK-6240 binding was greater in medial temporal cortex than in putamen. 18F-THK-5351 binding in medial temporal cortex was not different between amyloid-positive and amyloid-negative subjects (Mann Whitney U test, p = 0.171). 18F-MK-6240 binding was greater in medial temporal cortex in amyloid-positive than amyloid-negative subjects (p = 0.011). Lack of correlation in amyloid-negative subjects and high putamen binding suggest that 18F-THK-5351 binds a non-tau target not bound to 18F-MK-6240. Even in amyloid-positive patients, 18F-THK-5351 signal appears to be influenced more by off-target binding than by tau. 18F-MK-6240, in contrast, appears to be specific for tau pathology.