Dual tracer tau PET imaging reveals different molecular targets for (11)C-THK5351 and (11)C-PBB3 in the Alzheimer brain

PURPOSE: Several tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers ((11)C-THK5351 and (11)C-PBB3) in a head-to-head, in vivo, multimodal design. METHODS: Nine patients with a diagnosis of mild cognitive impairment or probable Alzheimer’s disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer’s disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers (11)C-THK5351 and (11)C-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer (11)C-AZD2184, a T1-MRI sequence, and neuropsychological assessment. RESULTS: The load and regional distribution of binding differed between (11)C-THK5351 and (11)C-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of (11)C-PBB3, but not that of (11)C-THK5351, in the temporal lobe resembled that of (11)C-AZD2184, with strong correlations detected between (11)C-PBB3 and (11)C-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with (11)C-THK5351 than with (11)C-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with (11)C-THK5351 than with (11)C-PBB3 binding. CONCLUSION: This research suggests different molecular targets for these tracers; while (11)C-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of (11)C-THK5351 fitted the expected distribution of tau pathology in Alzheimer’s disease better and was more closely related to downstream disease markers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00259-018-4012-5) contains supplementary material, which is available to authorized users.