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Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases

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Abstract

Purpose

In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer’s disease (AD).

Methods

Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum.

Results

SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient.

Conclusion

Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

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Acknowledgments

The authors acknowledge Life Molecular Imaging for providing the precursor for this study.

Funding

This study was funded by the NIH (K01-AG051718 and R21-AG058859, Mormino; R01-AG048076, Wagner; P50-AG047366, Henderson; R01-AG061120, Zeineh), General Electric (GE), the Stanford Wu Tsai Neuroscience Institute, and the Stanford Precision Health and Integrated Diagnostics Center.

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Authors and Affiliations

  1. Department of Neurology and Neurological Sciences, Stanford Medical School, 300 Pasteur Drive, Stanford, CA, 94305, USA

    Elizabeth C. Mormino, Tyler N. Toueg, Ayesha Nadiadwala, Nicole K. Corso, Jacob N. Hall, Sharon J. Sha, Gayle Deutsch, Michelle James, Carolyn A. Fredericks, Kathleen Poston & Michael D. Greicius

  2. Department of Radiology, Stanford Medical School, Stanford, CA, USA

    Carmen Azevedo, Jessica B. Castillo, Audrey Fan, Michelle James, Mary Ellen Koran, Michael Zeineh, Mehdi Khalighi, Guido A. Davidzon, Bin Shen, Greg Zaharchuk & Frederick T. Chin

  3. Department of Psychology, Stanford University, Stanford, CA, USA

    Wanjia Guo, Alexandra N. Trelle, Marc B. Harrison, Madison P. Hunt & Anthony D. Wagner

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  1. Elizabeth C. Mormino
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  2. Tyler N. Toueg
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Corresponding author

Correspondence to Elizabeth C. Mormino.

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Conflict of interest

Author Elizabeth Mormino receives research funds from the National Institutes of Health grants K01-AG051718 and R21-AG058859. Dr. Mormino has been a consultant for Eli Lilly, Biogen Idec, F Hoffmann-La Roche Ltd., Janssen, and Alector.

Author Michael Zeineh receives research funds from the National Institutes of Health grant R01-AG061120 and from General Electric (GE).

Michelle James reports travel compensation from World Molecular Imaging Congress (WMIC) to present on Emerging neuroimaging techniques and present at an educational session on “best practices for small animal PET imaging.”

Author Sharon Sha receives research support from Biogen Idec, F Hoffmann-La Roche Ltd., Genentech, and Novartis for her role as Investigator in Clinical Trials. Dr. Sha has been a consultant for Abelson Taylor, Baird, Clearview Healthcare Partners, SelfCare Catalysts Inc., and the University of Southern California. Dr. Sha is funded by National Institutes of Health grants P50 AG047366 (Stanford Alzheimer’s Disease Center) and R01 AG048076.

Author Greg Zaharchuk has received research support from GE Healthcare, LifeMI, Stanford AI Laboratory (SAIL), and the National Institutes of Health grants P50 AG047366. Dr. Zaharchuk has equity in Subtle Medical.

Author Anthony Wagner receives research funds from the National Institutes of Health grant R01-AG048076.

All other authors declare that he/she has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Mormino, E.C., Toueg, T.N., Azevedo, C. et al. Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases. Eur J Nucl Med Mol Imaging 48, 2233–2244 (2021). https://doi.org/10.1007/s00259-020-04923-7

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