Comparison of [18F]flortaucipir and [18F]MK6240 for the detection of tau pathology in Alzheimer's disease (HEAD): a multicentre, prospective, cross-sectional, within-participant study

Background Tau PET imaging has emerged as a critical biomarker for Alzheimer's disease, informing diagnosis, staging, and therapeutic selection. We investigated whether PET tracer selection alters tau detection. Methods We conducted a prospective, multicentre, non-randomised, within-participant comparison of [ 18 F]flortaucipir (Tauvid), currently used in clinical settings in the USA and Europe, and [ 18 F]MK6240, an investigational tau PET tracer. Participants were recruited from eight north American sites and underwent tau PET, amyloid-β (Aβ) PET, and detailed cognitive assessments. Tau PET with both agents was acquired within a 45-day window. Coprimary outcomes were the discriminative accuracy for Alzheimer's disease-related cognitive impairment and the frequency of tau positivity in early medial temporal lobe (MTL) and late neocortical regions. The study is registered with ClinicalTrials.gov, NCT05361382. Findings Between March 2, 2022, and Aug 27, 2025, 775 individuals were enrolled, with 682 completing all procedures (373 [55%] female, 309 [45%] male; 38 [6%] aged 19–27 years, 214 [31%] aged 50–65 years, and 430 [63%] aged 65–89 years). 32 (5%) participants identified as Hispanic or Latino. 637 (93%) identified as White, 24 (4%) as Black or African American, 16 (2%) as Asian, and five (1%) as other. In addition, 49 (7%) individuals were identified as being from a rural area. [ 18 F]MK6240 showed greater accuracy than [ 18 F]flortaucipir in distinguishing Alzheimer's disease from non-Alzheimer's disease impairment (area under the curve 0·93, 95% CI 0·89–0·95 vs 0·86, 0·75–0·91; p