Characterization of tau positron emission tomography tracer [18F]AV-1451 binding to postmortem tissue in Alzheimer's disease, primary tauopathies, and other dementias.
[en] ("[en] INTRODUCTION: Aggregation of tau is a hallmark of many neurodegenerative diseases, and tau imaging with positron emission tomography (PET) may allow early diagnosis and treatment monitoring. We assessed binding of the PET tracer [18F]AV-1451 in a range of dementias.
METHODS: Phosphorimaging was used to quantify binding to postmortem brain tissue from 33 patients with different, histopathologically characterized, neurodegenerative dementias.
RESULTS: [18F]AV-1451 showed high specific binding in cases with Alzheimer's disease (AD), moderate binding in Pick's disease and frontotemporal dementia with parkinsonism-17, and low but displaceable binding in corticobasal degeneration, progressive supranuclear palsy, non-tau proteinopathies, and in controls without pathology. Tracer binding did not correlate with tau load within disease groups.
DISCUSSION: [18F]AV-1451 binds to tau in AD, and some other tauopathies. However, evidence for a non-tau binding site and lack of correlation between tracer binding and antibody staining suggest that reliable quantification of tau load with this tracer is problematic.","[en] ","")
Disciplines :
Chemistry Radiology, nuclear medicine & imaging Neurology
Author, co-author :
Sander, Kerstin; Institute of Nuclear Medicine and Department of Chemistry, University College London, London, UK
Lashley, Tammaryn; Institute of Neurology, Department of Molecular Neuroscience, Queen Square Brain Bank, University College London, London, UK
Gami, Priya; Institute of Neurology, Department of Molecular Neuroscience, Queen Square Brain Bank, University College London, London, UK
Gendron, Thibault ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique-nucléaire ; Institute of Nuclear Medicine and Department of Chemistry, University College London, London, UK
Lythgoe, Mark F; Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, UK
Rohrer, Jonathan D; Institute of Neurology, Department of Neurodegenerative Disease, Dementia Research Centre, University College London, London, UK
Schott, Jonathan M; Institute of Neurology, Department of Neurodegenerative Disease, Dementia Research Centre, University College London, London, UK
Revesz, Tamas; Institute of Neurology, Department of Molecular Neuroscience, Queen Square Brain Bank, University College London, London, UK
Fox, Nick C; Institute of Neurology, Department of Neurodegenerative Disease, Dementia Research Centre, University College London, London, UK
Årstad, Erik; Institute of Nuclear Medicine and Department of Chemistry, University College London, London, UK. Electronic address: e.arstad@ucl.ac.uk
Language :
English
Title :
Characterization of tau positron emission tomography tracer [18F]AV-1451 binding to postmortem tissue in Alzheimer's disease, primary tauopathies, and other dementias.
Publication date :
November 2016
Journal title :
Alzheimer's and Dementia: the Journal of the Alzheimer's Association
ARUK - Alzheimer’s Research UK NIHR - National Institute for Health Research
Funding text :
The authors thank Avid Radiopharmaceuticals Inc. for providing labeling precursors and methods for the radiosynthesis of [ 18 F]AV-1451. The authors acknowledge funding by the Leonard Wolfson Experimental Neurology Centre (K.S. and P.G.), Alzheimer's Research UK (T.L.; ARUK-SRF2015-2), UCL Business (T.G.), and the NIHR Queen Square Dementia Biomedical Research Unit . This work was undertaken at UCLH/UCL, which is funded in part by the Department of Health's NIHR Biomedical Research Centres funding scheme.
[5] Cairns, N.J., Bigio, E.H., Mackenzie, I.R., Neumann, M., Lee, V.M., Hatanpaa, K.J., et al., Consortium for Frontotemporal Lobar Degeneration. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: Consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114 (2007), 5–22.
[6] Noble, W., Hanger, D.P., Miller, C.C., Lovestone, S., The importance of tau phosphorylation for neurodegenerative diseases. Front Neurol, 4, 2013, 83.
[8] Arriagada, P.V., Growdon, J.H., Hedley-Whyte, E.T., Hyman, B.T., Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 42 (1992), 631–639.
[9] Ossenkoppele, R., Schonhaut, D.R., Baker, S.L., O'Neil, J.P., Janabi, M., Ghosh, P.M., et al. Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy. Ann Neurol 77 (2015), 338–342.
[10] Xia, C.F., Arteaga, J., Chen, G., Gangadharmath, U., Gomez, L.F., Kasi, D., et al. [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement 9 (2013), 666–676.
[11] Chien, D.T., Szardenings, A.K., Bahri, S., Walsh, J.C., Mu, F., Xia, C., et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimers Dis 38 (2012), 171–184.
[12] Shah, M., Catafau, A.M., Molecular imaging insights into neurodegeneration: Focus on tau PET radiotracers. J Nucl Med 55 (2014), 871–874.
[13] Mirra, S.S., Heyman, A., McKeel, D., Sumi, S.M., Crain, B.J., Brownlee, L.M., et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41 (1991), 479–486.
[14] Braak, H., Braak, E., Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82 (1991), 239–259.
[15] Thal, D.R., Rueb, U., Orantes, M., Braak, H., Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58 (2000), 1791–1800.
[16] Montine, T.J., Phelps, C.H., Beach, T.G., Bigio, E.H., Cairns, N.J., Dickson, D.W., et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: A practical approach. Acta Neuropathol 123 (2012), 1–11.
[17] Dickson, D.W., Hauw, J.J., Agid, Y., Litvan, I., Progressive supranuclear palsy and corticobasal degeneration. Dickson, D.W., Weller, R.O., (eds.) Neurodegeneration: The molecular pathology of dementia and movement disorders, 2011, Wiley-Blackwell, Chichester, 135–155.
[18] Mackenzie, I.R., Neumann, M., Baborie, A., Sampathu, D.M., Du Plessis, D., Jaros, E., et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 122 (2011), 111–113.
[19] McKeith, I.G., Dickson, D.W., Lowe, J., Emre, M., O'Brien, J.T., Feldman, H., et al., Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium. Neurology 65 (2005), 1863–1872.
[20] Lashley, T., Rohrer, J.D., Bandopadhyay, R., Fry, C., Ahmed, Z., Isaacs, A.M., et al. A comparative clinical, pathological, biochemical and genetic study of fused in sarcoma proteinopathies. Brain 134:Pt 9 (2011), 2548–2564.
[21] Xiong, H., Hoye, A.T., Fan, K.H., Li, X., Clemens, J., Horchler, C.L., et al. Facile route to 2-fluoropyridines via 2-pyridyltrialkylammonium salts prepared from pyridine N-oxides and application to 18F-labeling. Org Lett 17 (2015), 3716–3729.
[22] Schneider, C.A., Rasband, W.S., Eliceiri, K.W., NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9 (2012), 671–675.
[23] de Silva, R., Lashley, T., Gibb, G., Hanger, D., Hope, A., Reid, A., et al. Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies. Neuropathol Appl Neurobiol 29 (2003), 288–302.
[24] Augustinack, J.C., Schneider, A., Mandelkow, E.M., Hyman, B.T., Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta Neuropathol 103 (2002), 26–35.
[25] Maruyama, M., Shimada, H., Suhara, T., Shinotoh, H., Ji, B., Maeda, J., et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79 (2013), 1094–1108.
[26] Varrone, A., Steiger, C., Schou, M., Takano, A., Finnema, S.J., Guilloteau, D., et al. In vitro autoradiography and in vivo evaluation in cynomolgus monkey of [18F]FE-PE21, a new dopamine transporter PET radioligand. Synapse 63 (2009), 871–880.
[27] Kanazawa, M., Shimohata, T., Toyoshima, Y., Tada, M., Kakita, A., Morita, T., et al. Cerebellar involvement in progressive supranuclear palsy: A clinicopathological study. Mov Disord 24 (2009), 1312–1318.
[29] Clavaguera, F., Akatsu, H., Fraser, G., Crowther, R.A., Frank, S., Hench, J., et al. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc Natl Acad Sci U S A 110 (2013), 9535–9540.
