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Head-to-Head Comparison of Tau-PET Radioligands for Imaging TDP-43 in Post-Mortem ALS Brain

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Abstract

Purpose

In vivo detection of transactivation response element DNA binding protein-43 kDa (TDP-43) aggregates through positron emission tomography (PET) would impact the ability to successfully develop therapeutic interventions for a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).  The purpose of the present study is to evaluate the ability of six tau PET radioligands to bind to TDP-43 aggregates in post-mortem brain tissues from ALS patients.

Procedures

Herein, we report the first head-to-head evaluation of six tritium labeled isotopologs of tau-targeting PET radioligands, [3H]MK-6240 (a.k.a. florquinitau), [3H]Genentech Tau Probe-1 (GTP-1), [3H]JNJ-64326067(JNJ-067), [3H]CBD-2115, [3H]flortaucipir, and [3H]APN-1607, and their ability to bind to the β-pleated sheet structures of aggregate TDP-43 in post-mortem ALS brain tissues by autoradiography and immunostaining methods. Post-mortem frontal cortex, motor cortex, and cerebellum tissues were evaluated, and binding intensity was aligned with areas of elevated phosphorylated tau (ptau), pTDP-43, and \(\beta\)-amyloid.

Results

Negligible binding was observed with [3H]MK-6240, [3H]JNJ-067, and [3H]GTP-1. While [3H]CBD-2115 displayed marginal specific binding, this binding did not significantly correlate with the distribution of pTDP-43 and AT8 inclusions. Of the remaining ligands, the distribution of [3H]flortaucipir did not significantly correlate to pTDP-43 pathology; however, specific binding trends to a positive relationship with tau. Finally, [3H]APN-1607 relates most strongly to amyloid load and does not indicate pTDP-43 pathology as confirmed by [3H]PiB distribution in sister sections.

Conclusions

Our results demonstrate the prominent nature of mixed pathology in ALS, and do not support the application of [3H]MK-6240, [3H]JNJ-067, [3H]GTP-1, [3H]CBD-2115, [3H]flortaucipir, or [3H]APN-1607 for selective imaging TDP-43 in ALS for clinical research with the currently available in vitro data. Identification of potent and selective radiotracers for TDP-43 remains an ongoing challenge.

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Abbreviations

TDP-43:

Transactivation response element DNA binding protein-43 kDa

pTDP-43:

Phosphorylated TDP-43

ALS:

Amyotrophic lateral sclerosis

ptau:

Phosphorylated tau

AD:

Alzheimer’s disease

PET:

Positron emission tomography

CNS:

Central nervous system

Cryo-EM:

Cryo-electron microscopy

FTLD:

Frontotemporal lobar degeneration

FTD:

Frontotemporal dementia

nM:

Nanomolar

µM:

Micromolar

JNJ-067:

JNJ-64326067

GTP-1:

Genentech Tau Probe-1

ARG:

Autoradiography

IHC:

Immunohistochemistry

References

  1. Chiò A, Logroscino G, Traynor BJ et al (2013) Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 41:118–130. https://doi.org/10.1159/000351153

    Article  PubMed  Google Scholar 

  2. Geser F, Martinez-Lage M, Robinson J et al (2009) Clinical and pathological continuum of multisystem TDP-43 proteinopathies. Arch Neurol 66:180–189. https://doi.org/10.1001/archneurol.2008.558

    Article  PubMed  PubMed Central  Google Scholar 

  3. Renton AE, Chiò A, Traynor BJ (2014) State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci 17:17–23. https://doi.org/10.1038/nn.3584

    Article  CAS  PubMed  Google Scholar 

  4. Majumder V, Gregory JM, Barria MA et al (2018) TDP-43 as a potential biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis. BMC Neurol 18:90. https://doi.org/10.1186/s12883-018-1091-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133. https://doi.org/10.1126/science.1134108

    Article  CAS  PubMed  Google Scholar 

  6. Arai T, Hasegawa M, Akiyama H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602–611. https://doi.org/10.1016/j.bbrc.2006.10.093

    Article  CAS  PubMed  Google Scholar 

  7. Feneberg E, Gray E, Ansorge O et al (2018) Towards a TDP-43-based biomarker for ALS and FTLD. Mol Neurobiol 55:7789–7801. https://doi.org/10.1007/s12035-018-0947-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kovacs GG, Botond G, Budka H (2010) Protein coding of neurodegenerative dementias: the neuropathological basis of biomarker diagnostics. Acta Neuropathol 119:389–408. https://doi.org/10.1007/s00401-010-0658-1

    Article  CAS  PubMed  Google Scholar 

  9. Brettschneider J, Del Tredici K, Toledo JB et al (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 74:20–38. https://doi.org/10.1002/ana.23937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tamara Seredenina P (2019) Discovery and development of diagnostics and therapeutics for TDP-43 proteinopathies. Lisbon, Portugal

  11. Brooks A, Tanzey S, Shao X, Scott P (2018) Binding potential of radioligand [18F]FL2-b by autoradiography in amyotrophic lateral sclerosis and lewy body dementia. J Nucl Med 59:613

    Google Scholar 

  12. Tanzey S, Brooks A, Shao X, Scott P (2020) Extraction of enriched phosphorylated TDP43 from ALS tissue for evaluation of new TDP-43 radiotracers. J Nucl Med 61:1038–1038

    Google Scholar 

  13. Kassubek J, Pagani M (2019) Imaging in amyotrophic lateral sclerosis: MRI and PET. Curr Opin Neurol 32:740–746. https://doi.org/10.1097/wco.0000000000000728

    Article  CAS  PubMed  Google Scholar 

  14. Harada R, Okamura N, Furumoto S, Yanai K (2018) Imaging protein misfolding in the brain using β-sheet ligands. Front Neurosci 12. https://doi.org/10.3389/fnins.2018.00585

  15. Klunk WE, Wang Y, Huang GF, et al (2001) Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. In: Life Sci. Netherlands, pp 1471–84

  16. Mathis CA, Mason NS, Lopresti BJ, Klunk WE (2012) Development of positron emission tomography β-amyloid plaque imaging agents. Semin Nucl Med 42:423–432

    Article  PubMed  PubMed Central  Google Scholar 

  17. Leuzy A, Chiotis K, Lemoine L et al (2019) Tau PET imaging in neurodegenerative tauopathies—still a challenge. Mol Psychiatry 24:1112–1134. https://doi.org/10.1038/s41380-018-0342-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jucker M, Walker LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501:45–51. https://doi.org/10.1038/nature12481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bigio EH, Wu JY, Deng HX et al (2013) Inclusions in frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP) and amyotrophic lateral sclerosis (ALS), but not FTLD with FUS proteinopathy (FTLD-FUS), have properties of amyloid. Acta Neuropathol 125:463–465

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kwong LK, Uryu K, Trojanowski JQ, Lee VM-Y (2008) TDP-43 proteinopathies: neurodegenerative protein misfolding diseases without amyloidosis. Neurosignals 16:41–51. https://doi.org/10.1159/000109758

    Article  CAS  PubMed  Google Scholar 

  21. Mompeán M, Hervás R, Xu Y et al (2015) Structural evidence of amyloid fibril formation in the putative aggregation domain of TDP-43. J Phys Chem Lett 6:2608–2615. https://doi.org/10.1021/acs.jpclett.5b00918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Robinson JL, Geser F, Stieber A, et al (2013) TDP-43 skeins show properties of amyloid in a subset of ALS cases. ActaNeuropathol 121–131. https://doi.org/10.1007/s00401-012-1055-8

  23. Li Q, Babinchak WM, Surewicz WK (2021) Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43. Nat Commun 12:1620. https://doi.org/10.1038/s41467-021-21912-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cao Q, Boyer DR, Sawaya MR et al (2019) Cryo-EM structures of four polymorphic TDP-43 amyloid cores. Nat Struct Mol Biol 26:619–627. https://doi.org/10.1038/s41594-019-0248-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bevan-Jones WR, Cope TE, Jones PS et al (2018) [18F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia. J Neurol Neurosurg Psychiatry 89:1032–1037. https://doi.org/10.1136/jnnp-2017-316402

    Article  CAS  PubMed  Google Scholar 

  26. Xia C-F, Arteaga J, Chen G et al (2013) [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimer’s Dement 9:666–676. https://doi.org/10.1016/j.jalz.2012.11.008

    Article  Google Scholar 

  27. Hostetler ED, Walji AM, Zeng Z et al (2016) Preclinical characterization of 18F-MK-6240, a promising PET tracer for in vivo quantification of human neurofibrillary tangles. J Nucl Med 57:1599–1606. https://doi.org/10.2967/jnumed.115.171678

    Article  CAS  PubMed  Google Scholar 

  28. Schmidt ME, Janssens L, Moechars D et al (2020) Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 47:3176–3185. https://doi.org/10.1007/s00259-020-04880-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sanabria Bohorquez S, Marik J, Ogasawara A et al (2019) [18F]GTP1 (Genentech Tau Probe 1), a radioligand for detecting neurofibrillary tangle tau pathology in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 46:2077–2089. https://doi.org/10.1007/s00259-019-04399-0

    Article  CAS  PubMed  Google Scholar 

  30. Shimada H, Kitamura S, Ono M et al (2017) [IC-P-198]: First-in-human PET study with 18F-AM-PBB3 and 18F-PM-PBB3. Alzheimer’s Dement 13:P146–P146. https://doi.org/10.1016/j.jalz.2017.06.2573

    Article  Google Scholar 

  31. Lindberg A, Knight AC, Sohn D et al (2021) Radiosynthesis, in vitro and in vivo evaluation of [18F]CBD-2115 as a first-in-class radiotracer for imaging 4R-tauopathies. ACS Chem Neurosci 12:596–602. https://doi.org/10.1021/acschemneuro.0c00801

    Article  CAS  PubMed  Google Scholar 

  32. Sohn D (2019) Selective ligands for tau aggregates. WIPOI Bureau, Karen and Sten Mortstedt CBD Solutions AB.

  33. Ono M, Sahara N, Kumata K et al (2017) Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies. Brain 140:764–780. https://doi.org/10.1093/brain/aww339

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tagai K, Ono M, Kubota M et al (2021) High-contrast in vivo imaging of tau pathologies in Alzheimer’s and non-Alzheimer’s disease tauopathies. Neuron 109:42-58.e8. https://doi.org/10.1016/j.neuron.2020.09.042

    Article  CAS  PubMed  Google Scholar 

  35. Murugan NA, Nordberg A, Ågren H (2018) Different positron emission tomography tau tracers bind to multiple binding sites on the tau fibril: insight from computational modeling. ACS Chem Neurosci 9:1757–1767. https://doi.org/10.1021/acschemneuro.8b00093

    Article  CAS  PubMed  Google Scholar 

  36. Rowe CC, Pejoska S, Mulligan RS et al (2013) Head-to-head comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-amyloid imaging in aging and dementia. J Nucl Med 54:880–886. https://doi.org/10.2967/jnumed.112.114785

    Article  CAS  PubMed  Google Scholar 

  37. Smith R, Santillo AF, Waldö ML et al (2019) 18F-Flortaucipir in TDP-43 associated frontotemporal dementia. Sci Rep 9:6082. https://doi.org/10.1038/s41598-019-42625-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tsai RM, Bejanin A, Lesman-Segev O et al (2019) 18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. Alzheimer’s Res Ther 11:13. https://doi.org/10.1186/s13195-019-0470-7

    Article  Google Scholar 

  39. 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. https://doi.org/10.1002/ana.24517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sander K, Lashley T, Gami P et al (2016) Characterization of tau positron emission tomography tracer [18F]AV-1451 binding to postmortem tissue in Alzheimer’s disease, primary tauopathies, and other dementias. Alzheimer’s Dement 12:1116–1124. https://doi.org/10.1016/j.jalz.2016.01.003

    Article  Google Scholar 

  41. Lowe VJ, Curran G, Fang P et al (2016) An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathol Commun 4:58. https://doi.org/10.1186/s40478-016-0315-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhou Y, Li J, Nordberg A, Ågren H (2021) Dissecting the binding profile of PET tracers to corticobasal degeneration tau fibrils. ACS Chem Neurosci 12:3487–3496. https://doi.org/10.1021/acschemneuro.1c00536

    Article  CAS  PubMed  Google Scholar 

  43. Lemoine L, Leuzy A, Chiotis K et al (2018) Tau positron emission tomography imaging in tauopathies: the added hurdle of off-target binding. Alzheimer’s Dement 10:232–236. https://doi.org/10.1016/j.dadm.2018.01.007

    Article  Google Scholar 

  44. Vermeiren C, Motte P, Viot D et al (2018) The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases. Mov Disord 33:273–281. https://doi.org/10.1002/mds.27271

    Article  CAS  PubMed  Google Scholar 

  45. Jie CVML, Treyer V, Schibli R, Mu L (2021) TauvidTM: The first FDA-approved PET tracer for imaging tau pathology in Alzheimer’s disease. Pharmaceuticals 14. https://doi.org/10.3390/ph14020110

  46. Jossan SS, Ekblom J, Aquilonius SM, Oreland L (1994) Monoamine oxidase-B in motor cortex and spinal cord in amyotrophic lateral sclerosis studied by quantitative autoradiography. J Neural Transm Suppl 41:243–248. https://doi.org/10.1007/978-3-7091-9324-2_31

    Article  CAS  PubMed  Google Scholar 

  47. James ML, Gambhir SS (2012) A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev 92:897–965. https://doi.org/10.1152/physrev.00049.2010

    Article  CAS  PubMed  Google Scholar 

  48. Wright JP, Goodman JR, Lin Y-G et al (2022) Monoamine oxidase binding not expected to significantly affect [18F]flortaucipir PET interpretation. Eur J Nucl Med Mol Imaging 49:3797–3808. https://doi.org/10.1007/s00259-022-05822-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Su Y, Fu J, Yu J et al (2020) Tau PET imaging with [18F]PM-PBB3 in frontotemporal dementia with MAPT mutation. J Alzheimers Dis 76:149–157. https://doi.org/10.3233/jad-200287

    Article  PubMed  Google Scholar 

  50. Ohta Y, Shimada H, Ikegami K et al (2021) A case of Kii amyotrophic lateral sclerosis/parkinsonism dementia complex presenting as progressive parkinsonism with corresponding tau imaging. Neurol Clin Neurosci 9:124–126. https://doi.org/10.1111/ncn3.12463

    Article  CAS  Google Scholar 

  51. Shi Y, Murzin AG, Falcon B et al (2021) Cryo-EM structures of tau filaments from Alzheimer’s disease with PET ligand APN-1607. Acta Neuropathol 141:697–708. https://doi.org/10.1007/s00401-021-02294-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Perez-Soriano A, Arena JE, Dinelle K et al (2017) PBB3 imaging in Parkinsonian disorders: evidence for binding to tau and other proteins. Mov Disord 32:1016–1024. https://doi.org/10.1002/mds.27029

    Article  CAS  PubMed  Google Scholar 

  53. Miranda-Azpiazu P, Svedberg M, Higuchi M et al (2020) Identification and in vitro characterization of C05–01, a PBB3 derivative with improved affinity for alpha-synuclein. Brain Res 1749:147131. https://doi.org/10.1016/j.brainres.2020.147131

    Article  CAS  PubMed  Google Scholar 

  54. Koga S, Ono M, Sahara N et al (2017) Fluorescence and autoradiographic evaluation of tau PET ligand PBB3 to α-synuclein pathology. Mov Disord 32:884–892. https://doi.org/10.1002/mds.27013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Das S, Zhang Z, Ang LC (2020) Clinicopathological overlap of neurodegenerative diseases: a comprehensive review. J Clin Neurosci 78:30–33. https://doi.org/10.1016/j.jocn.2020.04.088

    Article  PubMed  Google Scholar 

  56. Takeda T (2018) Possible concurrence of TDP-43, tau and other proteins in amyotrophic lateral sclerosis/frontotemporal lobar degeneration. Neuropathology 38:72–81. https://doi.org/10.1111/neup.12428

    Article  CAS  PubMed  Google Scholar 

  57. Hamilton RL, Bowser R (2004) Alzheimer disease pathology in amyotrophic lateral sclerosis. Acta Neuropathol 107:515–522. https://doi.org/10.1007/s00401-004-0843-1

    Article  PubMed  Google Scholar 

  58. Behrouzi R, Liu X, Wu D et al (2016) Pathological tau deposition in motor neurone disease and frontotemporal lobar degeneration associated with TDP-43 proteinopathy. Acta Neuropathol Commun 4:33. https://doi.org/10.1186/s40478-016-0301-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lyoo CH, Cho H, Choi JY et al (2016) (2016) Tau accumulation in primary motor cortex of variant Alzheimer’s disease with spastic paraparesis. J Alzheimers Dis 51:671–675. https://doi.org/10.3233/JAD-151052

    Article  CAS  PubMed  Google Scholar 

  60. Arseni D, Hasegawa M, Murzin AG et al (2022) Structure of pathological TDP-43 filaments from ALS with FTLD. Nature 601:139–143. https://doi.org/10.1038/s41586-021-04199-3

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Enigma Biomedical Group, Inc., and its affiliates (Cerveau Technologies and Meilleur Technologies) for the use of radiolabeled and/or unlabeled MK-6240, CBD-2115, and NAV-4694. We also thank Dr. Samuel Svensson from Oxiant Pharmaceuticals for the support with CBD-2115 and Target ALS for the post-mortem tissue samples. N.V. thanks the National Institute on Aging of the NIH (R01AG054473 and R01AG052414), Azrieli Foundation, Canada Foundation for Innovation, Ontario Research Fund, the Canada Research Chairs Program, and Takeda Pharmaceutical Company for the support. C.V. thanks the Canadian Institutes of Health Research (CIHR) for the receipt of the Canada Graduate Scholarship (Doctoral). C.D.M. acknowledges support from the CAMH Discovery Fund.

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  1. Ashley C. Knight and Christopher D. Morrone contributed to this work equally.

Authors and Affiliations

  1. Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Canada

    Ashley C. Knight, Christopher D. Morrone, Cassis Varlow, Wai Haung Yu & Neil Vasdev

  2. Institute of Medical Science, University of Toronto, 1 King’s College Circle, Toronto, Canada

    Ashley C. Knight, Cassis Varlow & Neil Vasdev

  3. Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle, Toronto, Canada

    Wai Haung Yu

  4. Takeda Pharmaceutical Company, Ltd, 35 Landsdowne Street, Cambridge, MA, USA

    Paul McQuade

  5. Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Canada

    Neil Vasdev

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Contributions

ACK, CDM, and CV performed the research and analyzed the data; ACK, CDM, CV, and NV wrote the manuscript; ACK, PM, and NV designed the study. ACK, CDM, CV, WHY, PM, and NV reviewed the manuscript.

Corresponding author

Correspondence to Neil Vasdev.

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All tissues were obtained in accordance with the guidelines put forth by the Centre for Addiction and Mental Health Research Ethics Board (protocol no. 036–2019).

Conflict of Interest

A.C.K. and P.M. are employed by Takeda Pharmaceutical Company. N.V. is a co-founder of MedChem Imaging, Inc. All authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

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Knight, A.C., Morrone, C.D., Varlow, C. et al. Head-to-Head Comparison of Tau-PET Radioligands for Imaging TDP-43 in Post-Mortem ALS Brain. Mol Imaging Biol 25, 513–527 (2023). https://doi.org/10.1007/s11307-022-01779-1

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