DOI: 10.1007/s00259-018-4012-5Pages: 1-13

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

1. Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Translational Alzheimer Neurobiology

2. Karolinska Institutet and Stockholm County Council, Department of Clinical Neuroscience, Center for Psychiatric Research

3. Karolinska University Hospital, Theme Aging

4. Stockholm University, Department of Psychology

5. Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics

6. Tohoku University, Cyclotron and Radioisotope Center

7. Tohoku Medical and Pharmaceutical University, Division of Pharmacology, Faculty of Medicine

8. National Institutes for Quantum and Radiological Science and Technology, National Institute of Radiological Sciences

Correspondence to:
Agneta Nordberg
Tel: +46 8 585 854 67
Email: Agneta.K.Nordberg@ki.se

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Abstract

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 (11C-THK5351 and 11C-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 11C-THK5351 and 11C-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer 11C-AZD2184, a T1-MRI sequence, and neuropsychological assessment.

Results

The load and regional distribution of binding differed between 11C-THK5351 and 11C-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of 11C-PBB3, but not that of 11C-THK5351, in the temporal lobe resembled that of 11C-AZD2184, with strong correlations detected between 11C-PBB3 and 11C-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with 11C-THK5351 than with 11C-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with 11C-THK5351 than with 11C-PBB3 binding.

Conclusion

This research suggests different molecular targets for these tracers; while 11C-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of 11C-THK5351 fitted the expected distribution of tau pathology in Alzheimer’s disease better and was more closely related to downstream disease markers.

This article is freely available, click here to access the full text/PDF

  • Accepted: Apr 6, 2018
  • Online: May 12, 2018

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