Skip to main content
SpringerLink
Log in

MAO-B Inhibitors Do Not Block In Vivo Flortaucipir([18F]-AV-1451) Binding

  • Brief Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

Recent evidence suggests that the tau radiotracer [18F]THK-5351 displays high affinity for the monoamine oxidase type B (MAO-B) enzyme. Utilizing another tau-tracer, flortaucipir ([18F]AV-1451), we previously reported that non-demented Parkinson’s disease patients show off-target binding in subcortical structures, but no appreciable cortical uptake. However, 59 % of these patients were receiving MAO-B inhibitors at the time of their scan. Here, we retrospectively investigated if MAO-B inhibitors in clinical doses affect flortaucipir binding.

Procedures

We compared the standard uptake values of flortaucipir at regional and voxel levels in Parkinson’s disease patients who received MAO-B inhibitors with those who did not.

Results

Sixteen of 27 Parkinson’s disease patients received MAO-B inhibitors at the time of scan. We found no significant flortaucipir uptake differences between the groups at voxel or regional levels.

Conclusion

Use of MAO-B inhibitors at pharmaceutical levels did not significantly affect flortaucipir binding. Thus, MAO-B does not appear to be a significant binding target of flortaucipir.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Johnson KA, Schultz A, Betensky RA et al (2016) Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol 79:110–119

    Article  PubMed  Google Scholar 

  2. Schöll M, Lockhart SN, Schonhaut DR et al (2016) PET imaging of tau deposition in the aging human brain. Neuron 89:971–982

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cho H, Choi JY, Hwang MS et al (2016) Tau PET in Alzheimer disease and mild cognitive impairment. Neurology 87:375–383

    Article  CAS  PubMed  Google Scholar 

  4. Pontecorvo MJ, Devous MD, Navitsky M et al (2017) Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain 140:748–763

    PubMed  PubMed Central  Google Scholar 

  5. Hansen AK, Knudsen K, Lillethorup TP et al (2016) In vivo imaging of neuromelanin in Parkinson’s disease using 18F-AV-1451 PET. Brain 139:2039–2049

    Article  PubMed  Google Scholar 

  6. Passamonti L, Vázquez Rodríguez P, Hong YT et al (2017) 18F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy. Brain 140:781–791

    PubMed  PubMed Central  Google Scholar 

  7. Marquié M, Normandin MD, Vanderburg CR et al (2015) Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol 78:787–800

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ng KP, Pascoal TA, Mathotaarachchi S et al (2017) Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain. Alzheimers Res Ther 9:25

    Article  PubMed  PubMed Central  Google Scholar 

  9. Carter SF, Scholl M, Almkvist O et al (2012) Evidence for Astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-Deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med 53:37–46

    Article  CAS  PubMed  Google Scholar 

  10. Tong J, Meyer JH, Furukawa Y et al (2013) Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies. J Cereb Blood Flow Metab 33:863–871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hansen AK, Damholdt MF, Fedorova TD et al (2017) In vivo cortical tau in Parkinson’s disease using 18F-AV-1451 positron emission tomography. Mov Disord 32:922–927

    Article  CAS  PubMed  Google Scholar 

  12. Xia CF, Arteaga J, Chen G et al (2013) [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimers Dement 9:666–676

    Article  PubMed  Google Scholar 

  13. Vermeiren C, Mercier J, Viot D et al (2015) T807, a reported selective tau tracer, binds with nanomolar affinity to monoamine oxidase a. Alzheimers Dement 11:P283

    Article  Google Scholar 

  14. Lowe VJ, Curran G, Fang P et al (2016) An autoradiographic evaluation of AV-1451 tau PET in dementia. Acta Neuropathol Commun 4:58

    Article  PubMed  PubMed Central  Google Scholar 

  15. Marquié M, Normandin MD, Meltzer AC et al (2017) Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies. Ann Neurol 81:117–128

    Article  PubMed  PubMed Central  Google Scholar 

  16. Smith R, Schöll M, Honer M et al (2017) Tau neuropathology correlates with FDG-PET, but not AV-1451-PET, in progressive supranuclear palsy. Acta Neuropathol 133:149–151

    Article  PubMed  Google Scholar 

  17. Nag S, Fazio P, Lehmann L et al (2016) In vivo and in vitro characterization of a novel MAO-B inhibitor Radioligand, 18F-labeled deuterated Fluorodeprenyl. J Nucl Med 57:315–320

    Article  CAS  PubMed  Google Scholar 

  18. Lockhart SN, Baker SL, Okamura N et al (2016) Dynamic PET measures of tau accumulation in cognitively normal older adults and Alzheimer’s disease patients measured using [18F] THK-5351. PLoS One 11:1–16

    Article  Google Scholar 

  19. Ikonomovic MD, Abrahamson EE, Price JC et al (2016) [F-18]AV-1451 positron emission tomography retention in choroid plexus: more than “off-target” binding. Ann Neurol 80:307–308

    Article  PubMed  PubMed Central  Google Scholar 

  20. Cho H, Choi JY, Hwang MS et al (2017) Subcortical 18F-AV-1451 binding patterns in progressive supranuclear palsy. Mov Disord 32:134–140

    Article  CAS  PubMed  Google Scholar 

  21. Whitwell JL, Lowe VJ, Tosakulwong N et al (2017) [18F]AV-1451 tau positron emission tomography in progressive supranuclear palsy. Mov Disord 32:124–133

    Article  CAS  PubMed  Google Scholar 

  22. Smith R, Schain M, Nilsson C et al (2017) Increased basal ganglia binding of (18) F-AV-1451 in patients with progressive supranuclear palsy. Mov Disord 32:108–114

    Article  CAS  PubMed  Google Scholar 

  23. Cho H, Choi JY, Lee SH et al (2017) 18F-AV-1451 binds to putamen in multiple system atrophy. Mov Disord 32:171–173

    Article  PubMed  Google Scholar 

  24. Shcherbinin S, Schwarz AJ, Joshi A et al (2016) Kinetics of the tau PET tracer 18F-AV-1451 (T807) in subjects with normal cognitive function, mild cognitive impairment, and Alzheimer disease. J Nucl Med 57:1535–1542

    Article  CAS  PubMed  Google Scholar 

  25. Zecca L, Fariello R, Riederer P et al (2002) The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson’s disease. FEBS Lett 510:216–220

    Article  CAS  PubMed  Google Scholar 

  26. Zecca L, Bellei C, Costi P et al (2008) New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals. Proc Natl Acad Sci U S A 105:17567–17572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fowler JS, Logan J, Wang G-J, Volkow ND (2003) Monoamine oxidase and cigarette smoking. Neurotoxicology 24:75–82

    Article  CAS  PubMed  Google Scholar 

  28. Nakamura S, Kawamata T, Akiguchi I et al (1990) Expression of monoamine oxidase B activity in astrocytes of senile plaques. Acta Neuropathol 80:419–425

    Article  CAS  PubMed  Google Scholar 

  29. Fowler JS, Volkow ND, Wang GJ et al (1996) Brain monoamine oxidase a inhibition in cigarette smokers. Proc Natl Acad Sci U S A 93:14065–14069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fowler JS, MacGregor RR, Wolf AP et al (1987) Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET. Science 235:481–485

    Article  CAS  PubMed  Google Scholar 

  31. Jensen SB, Olsen AK, Pedersen K, Cumming P (2006) Effect of monoamine oxidase inhibition on amphetamine-evoked changes in dopamine receptor availability in the living pig: a dual tracer PET study with [11C]harmine and [11C]raclopride. Synapse 59:427–434

    Article  CAS  PubMed  Google Scholar 

  32. Ginovart N, Meyer JH, Boovariwala A et al (2006) Positron emission tomography quantification of [11C]-harmine binding to monoamine oxidase-A in the human brain. J Cereb Blood Flow Metab 26:330–344

    Article  CAS  PubMed  Google Scholar 

  33. Fowler JS, Volkow ND, Logan J et al (1994) Slow recovery of human brain MAO B after L-deprenyl (Selegeline) withdrawal. Synapse 18:86–93

    Article  CAS  PubMed  Google Scholar 

  34. Arnett CD, Fowler JS, MacGregor RR et al (1987) Turnover of brain monoamine oxidase measured in vivo by positron emission tomography using L-[11C]deprenyl. J Neurochem 49:522–527

    Article  CAS  PubMed  Google Scholar 

  35. Lemoine L, Saint-Aubert L, Nennesmo I et al (2017) Cortical laminar tau deposits and activated astrocytes in Alzheimer’s disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography. Sci Rep 7:45496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Avid Radiopharmaceuticals, Inc. for providing precursor for the radiochemical tracer synthesis.

Funding

This study was financed through a grant from the Lundbeck Foundation.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and PET-Centre, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, bld. 10G, DK-8000, Aarhus C, Denmark

    Allan K. Hansen, David J. Brooks & Per Borghammer

  2. Division of Neuroscience, Department of Medicine, Imperial College London, London, UK

    David J. Brooks

  3. Division of Neuroscience, Newcastle University, Newcastle, UK

    David J. Brooks

Authors
  1. Allan K. Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David J. Brooks
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Per Borghammer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Allan K. Hansen.

Ethics declarations

Conflict of Interest

Allan K. Hansen—none. Per Borghammer has a consultancy with F. Hoffman-La Roche and has received grant support from Lundbeck foundation, Jascha foundation, the Danish Parkinson Foundation, and Aarhus University (Ph.D. salaries). David J Brooks has served on the Neuroscience and Mental Health Board of the Medical Research Council, UK; he is an associate editor of Brain and serves or has served as an editorial board member for Parkinsonism and Related Disorders, Journal of Parkinson’s Disease, Journal of Neural Transmission, Movement Disorders, Journal of Neurology, Neurosurgery and Psychiatry, and Synapse; he has received honoraria from TEVA, Orion Pharma, GlaxoSmithKline, Genentech, and Elan; he holds stock options and is a consultant for GE Healthcare and receives research support from the EU FP7 program, Alzheimer’s Research Trust UK, Parkinson’s UK, the Medical Research Council, UK, Danish Council for Independent Research, and the Lundbeck Foundation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hansen, A.K., Brooks, D.J. & Borghammer, P. MAO-B Inhibitors Do Not Block In Vivo Flortaucipir([18F]-AV-1451) Binding. Mol Imaging Biol 20, 356–360 (2018). https://doi.org/10.1007/s11307-017-1143-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-017-1143-1

Key words

Search

Navigation