Detection of tau spatial extent using MK6240 and flortaucipir PET

INTRODUCTION: Tau PET enables in vivo quantification of neurofibrillary tangle spread, yet whether tau spatial extent (TSE) performs comparably across tracers remains unknown. METHODS: We performed a head-to-head comparison of Flortaucipir and MK6240 tau PET in 682 individuals across the AD continuum, quantifying TSE as the percentage of regional voxels exceeding a tracer-specific abnormality threshold and evaluated it as a metric of tracer comparability. RESULTS: MK6240 showed greater TSE than Flortaucipir (CU Aβ+, medial temporal lobe [MTL]: 42% vs 25%; dementia Aβ+, late neocortical: 55% vs 42%), reaching 50% detection probability at lower Aβ burden (Centiloid: MTL, 26 vs 45; late neocortical, 95 vs 118). TSE showed higher associations than SUVR with memory, Aβ PET, and plasma pTau217, particularly in the neo-late composite. Participants with intermediate tau involvement (TSE 25–50%), most below the SUVR positivity thresholds (MTL positivity 10.2–16.9%), had approximately three-fold higher odds of Aβ PET and pTau217 positivity than TSE 0-25% (ORs 2.90–3.46). 53.4% of intermediate Flortaucipir cases (TSE 25–50%) shifted to a higher MK6240 category, and 82.5% of moderately high Flortaucipir cases (50–75%) were classified as near-saturated (75–100%) by MK6240. Neither raw TSE nor raw SUVR was directly interchangeable across tracers, with systematic and proportional bias for both metrics (MTL Deming slope: TSE 1.29; SUVR 2.69). DISCUSSION: TSE showed stronger unadjusted associations than SUVR in selected region- and outcome-specific comparisons, supporting its potential as a complementary measure. Like SUVR, raw TSE values were not directly interchangeable between flortaucipir and MK6240, and tracer-specific calibration and validation are required before cross-tracer use.

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Journal
medRxiv
Published
2026-10-28
DOI
https://doi.org/10.64898/2026.10.26.26366488
Primary Topic
Dementia and Cognitive Impairment Research
Type
preprint

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preprint

Detection of tau spatial extent using MK6240 and flortaucipir PET

Val J. Lowe, Dana Tudorascu, Tharick Ali Pascoal, Marina Scop Medeiros et al.
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medRxiv
Dementia and Cognitive Impairment Research
preprint

Detection of tau spatial extent using MK6240 and flortaucipir PET

Val J. Lowe, Dana Tudorascu, Tharick Ali Pascoal, Marina Scop Medeiros, Juan Fortea, Guilherme Povala, Douglas Teixeira Leffa, Belén Pascual, Joseph C. Masdeu, Guilherme Bauer‐Negrini, Pâmela C.L. Ferreira, Emma Patrice Ruppert, Arthur C. Macedo, Thomas K. Karikari, Bruna Bellaver, David N. Soleimani‐Meigooni, Suzanne L. Baker, Firoza Zubeida Lussier, Lívia Amaral, Cécile Tissot, Brian Andrew Gordon, Pedro Rosa‐Neto, Hwamee Oh, the HEAD Study
preprint en

Abstract

INTRODUCTION: Tau PET enables in vivo quantification of neurofibrillary tangle spread, yet whether tau spatial extent (TSE) performs comparably across tracers remains unknown. METHODS: We performed a head-to-head comparison of Flortaucipir and MK6240 tau PET in 682 individuals across the AD continuum, quantifying TSE as the percentage of regional voxels exceeding a tracer-specific abnormality threshold and evaluated it as a metric of tracer comparability. RESULTS: MK6240 showed greater TSE than Flortaucipir (CU Aβ+, medial temporal lobe [MTL]: 42% vs 25%; dementia Aβ+, late neocortical: 55% vs 42%), reaching 50% detection probability at lower Aβ burden (Centiloid: MTL, 26 vs 45; late neocortical, 95 vs 118). TSE showed higher associations than SUVR with memory, Aβ PET, and plasma pTau217, particularly in the neo-late composite. Participants with intermediate tau involvement (TSE 25–50%), most below the SUVR positivity thresholds (MTL positivity 10.2–16.9%), had approximately three-fold higher odds of Aβ PET and pTau217 positivity than TSE 0-25% (ORs 2.90–3.46). 53.4% of intermediate Flortaucipir cases (TSE 25–50%) shifted to a higher MK6240 category, and 82.5% of moderately high Flortaucipir cases (50–75%) were classified as near-saturated (75–100%) by MK6240. Neither raw TSE nor raw SUVR was directly interchangeable across tracers, with systematic and proportional bias for both metrics (MTL Deming slope: TSE 1.29; SUVR 2.69). DISCUSSION: TSE showed stronger unadjusted associations than SUVR in selected region- and outcome-specific comparisons, supporting its potential as a complementary measure. Like SUVR, raw TSE values were not directly interchangeable between flortaucipir and MK6240, and tracer-specific calibration and validation are required before cross-tracer use.

medRxiv
Houston Methodist (US), Lawrence Berkeley National Laboratory (US), University of Pittsburgh (US), John Brown University (US), University of California, San Francisco (US), Washington University in St. Louis (US), Hospital de Sant Pau (ES), Mayo Clinic in Arizona (US), Institut de Recerca Sant Pau (ES), UCSF Edward and Pearl Fein Memory and Aging Center (US), Houston Methodist Research Institute (US)
Alzheimer's Association, Weston Brain Institute, Fundación Tatiana Pérez de Guzmán el Bueno, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Canadian Institutes of Health Research, European Regional Development Fund, National Institute on Aging
Good health and well-being
Dementia and Cognitive Impairment Research
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