Tau Positron Emission Tomography (PET) Imaging: Past, Present, and Future

Journal of Medicinal Chemistry

Volumn 58, Issue 11, 2015, Pages 4365-4382

  Ariza, Manuela ^a   Kolb, Hartmuth C ^a   Moechars, Dieder ^a   Rombouts, Frederik ^a   Andrés, José Ignacio ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

RADIOLIGAND; TAU PROTEIN; TRACER; RADIOPHARMACEUTICAL AGENT;

BINDING AFFINITY; DRUG IDENTIFICATION; HUMAN; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PROTEIN AGGREGATION; REVIEW; ALZHEIMER DISEASE; ANIMAL; DIAGNOSTIC USE; METABOLISM; SCINTISCANNING;

ALZHEIMER DISEASE; ANIMALS; HUMANS; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS; TAU PROTEINS;

EID: 84931274846     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5017544     Document Type: Review

References (136)

1. Khachaturian, Z. S. Diagnosis of Alzheimers disease Arch. Neurol. 1985, 42, 1097-1105
2. Citron, M. Alzheimers disease: strategies for disease modification Nat. Rev. Drug Discovery 2010, 9, 387-398
3. Alzheimers Association. www.alz.org.
4. Anand, R.; Dip Gill, K.; Ali Mahdi, A. Therapeutics of Alzheimers disease: past, present and future Neuropharmacology 2014, 76, 27-50
5. Fargo, K.; Bleiler, L. Alzheimers Association report Alzheimers Dementia 2014, 10, e47-e92
6. Jack, C. R.; Albert, M. S.; Knopman, D. S.; McKhann, G. M.; Sperling, R. A.; Carrillo, M. C.; Thies, B.; Phelps, C. H. Introduction to the recommendations from the National Institute on Aging-Alzheimers Association workgroups on diagnostic guidelines for Alzheimers disease Alzheimers Dementia 2011, 7, 257-262
7. McKhann, G. M.; Knopman, D. S.; Chertkow, H.; Hyman, B. T.; Jack, C. R.; Kawash, C. H.; Klunk, W. E.; Koroshetz, W. J.; Manly, J. J.; Mayeux, R.; Mohs, R. C.; Morris, J. C.; Rossor, M. N.; Scheltens, P.; Carrillo, M. C.; Thies, B.; Weintraub, S.; Phelps, C. H. The diagnosis of dementia due to Alzheimers disease: recommendations from the National Institute on Aging-Alzheimers Association workgroups on diagnostic guidelines for Alzheimers disease Alzheimers Dementia. 2011, 7, 263-269
8. Albert, M. S.; DeKosky, S. T.; Dickson, D.; Dubois, B.; Feldman, H. H.; Fox, N. C.; Gamst, A.; Holtzman, D. M.; Jagust, W. J.; Petersen, R. C.; Snyder, P. J.; Carrillo, M. C.; Thies, B.; Phelps, C. H. The diagnosis of mild cognitive impairment due to Alzheimers disease: recommendations from the National Institute on Aging-Alzheimers Association workgroups on diagnostic guidelines for Alzheimers disease Alzheimers Dementia 2011, 7, 270-279
9. Sperling, R. A.; Aisen, P. S.; Beckett, L. A.; Bennett, D. A.; Craft, S.; Fagan, A. M.; Iwatsubo, T.; Jack, C. R.; Kaye, J.; Montine, T. J.; Park, D. C.; Reiman, E. M.; Rowe, C. C.; Siemers, E.; Stern, Y.; Yaffe, K.; Carrillo, M. C.; Thies, B.; Morrison-Bogorad, M.; Wagster, M. V.; Phelps, C. H. Toward defining the preclinical stages of Alzheimers disease: recommendations from the National Institute on Aging-Alzheimers Association workgroups on diagnostic guidelines for Alzheimers disease Alzheimers Dementia 2011, 7, 280-292
10. Braak, H.; Braak, E. Neuropathological stageing of Alzheimer-related changes Acta Neuropathol. 1991, 82, 239-259
11. Braak, H.; Braak, E. Frequency of stages of Alzheimer-related lesions in different age categories Neurobiol. Aging 1997, 18, 351-357
12. Delacourte, A. Diagnosis of Alzheimers disease Ann. Biol. Clin. 1998, 56, 133-142
13. Trojanowski, J. Q.; Clark, C. M.; Schmidt, M. L.; Arnold, S. E.; Lee, V. M. Strategies for improving the postmortem neuropathological diagnosis of Alzheimers disease Neurobiol. Aging 1997, 18, S75-S79
14. Karran, E.; Mercken, M.; De Strooper, B. The amyloid cascade hypothesis for Alzheimers disease: an appraisal for the development of therapeutics Nat. Rev. Drug Discovery 2011, 10 (9) 698-712
15. Dubois, B.; Feldman, H. H.; Jacova, C.; DeKosky, S. T.; Barberger-Gateau, P.; Cummings, J.; Delacourte, A.; Galasko, D.; Gauthier, S.; Jicha, G.; Meguro, K.; OBrien, J.; Pasquier, F.; Robert, P.; Rossor, M.; Salloway, S.; Stern, Y.; Visser, P. J.; Scheltens, P. Research criteria for the diagnosis of Alzheimers disease: revising the NINCDS-ADRDA criteria Lancet Neurol. 2007, 6, 734-746
16. Isaac, M.; Vamvakas, S.; Abadie, E.; Jonsson, B.; Gispen, C.; Pani, L. Qualification opinion of novel methodologies in the predementia stage of Alzheimers disease: cerebro-spinal-fluid related biomarkers for drugs affecting amyloid burden-regulatory considerations by European Medicines Agency focusing in improving benefit/risk in regulatory trials Eur. Neuropsychopharmacol. 2011, 21, 781-788
17. Blennow, K.; Hampel, H.; Zetterberg, H. Biomarkers in amyloid-β immunotherapy trials in Alzheimers disease Neuropsychopharmacology 2014, 39, 189-201
18. Zetterberg, H.; Tullhög, K.; Hansson, O.; Minthon, L.; Londos, E.; Blennow, K. Low incidence of post-lumbar puncture headache in 1,089 consecutive memory clinic patients Eur. Neurol. 2010, 63, 326-330
19. DeKosky, S. T.; Marek, K. Looking backward to move forward: early detection of neurodegenerative disorders Science 2003, 302, 830-834
20. Reiman, E. M.; Jagust, W. J. Brain imaging in the study of Alzheimers disease NeuroImage 2012, 61, 505-516
21. Zhou, M.; Wang, X.; Liu, Z.; Yu, L.; Hu, S.; Chen, L.; Zeng, W. Advances of molecular imaging probes for the diagnosis of Alzheimers disease Curr. Alzheimer Res. 2014, 11, 221-231
22. Valk, P. E.; Bailey, D. L.; Townsend, D. W.; Maisey, M. N. Positron Emission Tomography: Basic Science; Springer: New York, 2005.
23. Matthews, P. M.; Rabiner, E. A.; Passchier, J.; Gunn, R. N. Positron emission tomography molecular imaging for drug development Br. J. Clin. Pharmacol. 2011, 73, 175-186
24. Piel, M.; Vernaleken, I.; Rösch, F. Positron emission tomography in CNS drug discovery and drug monitoring J. Med. Chem. 2014, 57, 9232-9258
25. Kung, H. F. The β-amyloid hypothesis in Alzheimers disease: seeing is believing ACS Med. Chem. Lett. 2012, 3, 265-267
26. Mason, N. S.; Mathis, C. A.; Klunk, W. E. Positron emission tomography radioligands for in vivo imaging of Aβ plaques J. Labelled Compd. Radiopharm. 2013, 56, 89-95
27. Noël, S.; Cadet, S.; Gras, E.; Hureau, C. The benzazole scaffold: a SWAT to combat Alzheimers disease Chem. Soc. Rev. 2013, 42, 7747-7762
28. Rowe, C. C.; Villemagne, V. L. Amyloid imaging with PET in early Alzheimer disease diagnosis Med. Clin. North Am. 2013, 97, 377-398
29. Holland, J. P.; Liang, S. H.; Rotstein, B. H.; Collier, T. L.; Stephenson, N. A.; Greguric, I.; Vasdev, N. Alternative approaches for PET radiotracer development in Alzheimers disease: imaging beyond plaque J. Labelled Compd. Radiopharm. 2014, 57, 323-331
30. Klunk, W. E.; Engler, H.; Nordberg, A.; Wang, Y.; Blomqvist, G.; Holt, D. P.; Bergström, M.; Savitcheva, I.; Huang, G. F.; Estrada, S.; Ausén, B.; Debnath, M. L.; Barletta, J.; Price, J. C.; Sandell, J.; Lopresti, B. J.; Wall, A.; Koivisto, P.; Antoni, G.; Mathis, C. A.; Langström, B. Imaging brain amyloid in Alzheimers disease with Pittsburgh compound-B Ann. Neurol. 2004, 55, 306-319
31. Cohen, A. D.; Rabinovici, G. D.; Mathis, C. A.; Jagust, W. J.; Klunk, W. E.; Ikonomovic, M. D. Using Pittsburgh compound B for in vivo PET imaging of fibrillar amyloid-beta Adv. Pharmacol. 2012, 64, 27-81
32. Zhang, W.; Oya, S.; Kung, M.-P.; Hou, C.; Maier, D. L.; Kung, H. F. F-18 polyethyleneglycol stilbenes as PET imaging agents targeting Aβ aggregates in the brain Nucl. Med. Biol. 2005, 32, 799-809
33. Dollé, F. Carbon-11 and fluorine-18 chemistry devoted to molecular probes for imaging the brain with positron emission tomography J. Labelled Compd. Radiopharm. 2013, 56, 65-67
34. Serdons, K.; Verduyckt, T.; Vanderghinste, D.; Cleynhens, J.; Borghgraef, P.; Vermaelen, P.; Terwinghe, C.; Van Leuven, F.; Van Laere, K.; Kung, H.; Bormans, G.; Verbruggen, A. Synthesis of 18F-labeled 2-(4'-fluorophenyl)-1,3-benzothiazole and evaluation as amyloid imaging agent in comparison with [11C]-PIB Bioorg. Med. Chem. Lett. 2009, 19, 602-605
35. Jureus, A.; Swahn, B.-M.; Sandell, J.; Jeppsson, F.; Johnson, A. E.; Johnstroem, P.; Neelissen, J. A. M.; Sunnemark, D.; Farde, L.; Svensson, S. P. S. Characterization of AZD4694, a novel fluorinated Aβ plaque neuroimaging PET radioligand J. Neurochem. 2010, 114, 784-794
36. Landau, S. M.; Thomas, B. A.; Thurfjell, L.; Schmidt, M.; Margolin, R.; Mintun, M.; Pontecorvo, M.; Baker, S. L.; Jagust, W. J. Amyloid PET imaging in Alzheimers disease: a comparison of three radiotracers Eur. J. Nucl. Med. Mol. Imaging 2014, 41, 1398-1407
37. Rowe, C. C.; Pejoska, S.; Mulligan, R. S.; Jones, G.; Chan, J. G.; Svensson, S.; Cselényi, Z.; Masters, C. L.; Villemagne, V. L. Head-to-head comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-amyloid imaging in aging and dementia J. Nucl. Med. 2013, 54, 880-886
38. Kepe, V.; Moghbel, M. C.; Langström, B.; Zaidi, H.; Vinters, H. V.; Huang, S.-C.; Satyamurthy, N.; Doudeet, D.; Mishani, E.; Cohen, R. M.; Hoilund-Carlsen, P. F.; Alavi, A.; Barrio, J. R. Amyloid-β positron emission tomography imaging probes: a critical review J. Alzheimers Dis. 2013, 36, 613-631
39. Eckroat, T. J.; Mayhoub, A. S.; Garneau-Tsodikova, S. Amyloid-β probes: review of structure-activity and brain-kinetics relationships Beilstein J. Org. Chem. 2013, 9, 1012-1044
40. Villemagne, V. L.; Furumoto, S.; Fodero-Tavoletti, M.; Harada, R.; Mulligan, R. S.; Kudo, Y.; Masters, C. L.; Yanai, K.; Rowe, C. C.; Okamura, N. The challenges of tau imaging Future Neurol. 2012, 7, 409-421
41. Sperling, R. A.; Aisen, P. S.; Beckett, L. A.; Bennett, D. A.; Craft, S.; Fagan, A. M.; Iwatsubo, T.; Jack, C. R., Jr.; Kaye, J.; Montine, T. J.; Park, D. C.; Reiman, E. M.; Rowe, C. C.; Siemers, E.; Stern, Y.; Yaffe, K.; Carrillo, M. C.; Thies, B.; Morrison-Bogorad, M.; Wagster, M. V.; Phelps, C. H. Toward defining the preclinical stages of Alzheimers disease: recommendations from the National Institute on Aging and the Alzheimers Association workgroups on diagnostic guidelines for Alzheimers disease Alzheimers Dementia 2011, 7, 280-292
42. U.S. Food and Drug Administration. www.fda.gov.
43. Maccioni, R. B.; Farías, G.; Morales, I.; Navarrete, L. The revitalized tau hypothesis on Alzheimers disease Arch. Med. Res. 2010, 41, 226-231
44. Arriagada, P. V.; Growdon, J. H.; Hedley-Whyte, E. T.; Hyman, B. T. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimers disease Neurology 1992, 42, 631-639
45. Ke, Y. D.; Suchowerska, A. K.; van der Hoven, J.; De Silva, D. M.; Wu, C. W.; van Eersel, J.; Ittner, A.; Ittner, L. M. Lessons from tau-deficient mice Int. J. Alzheimers Dis. 2012, 2012, 873270
46. Medeiros, R.; Baglietto-Vargas, D.; LaFerla, F. M. The role of tau in Alzheimers disease and related disorders CNS Neurosci. Ther. 2011, 17, 514-524
47. Villemagne, V. L.; Okamura, N. In vivo tau imaging: obstacles and progress Alzheimers Dementia 2014, 10, S254-S264
48. Shah, M.; Catafau, A. M. Molecular imaging insights into neurodegeneration: focus on tau PET radiotracers J. Nucl. Med. 2014, 55, 871-874
49. Mach, R. H. New targets for the development of PET tracers for imaging neurodegeneration in Alzheimer disease J. Nucl. Med. 2014, 55, 1221-1224
50. Zimmer, E. R.; Leuzy, A.; Gauthier, S.; Rosa-Neto, P. Developments in tau PET imaging Can. J. Neurol. Sci. 2014, 41, 547-553
51. Villemagne, V. L.; Fodero-Tavoletti, M. T.; Masters, C. L.; Rowe, C. C. Tau imaging: early progress and future directions Lancet Neurol. 2015, 14, 114-124
52. Okamura, N.; Harada, R.; Furumoto, S.; Arai, H.; Yanai, K.; Kudo, Y. Tau PET imaging in Alzheimers disease Curr. Neurol. Neurosci. Rep. 2014, 14, 500
53. Weingarten, M. D.; Lockwood, A. H.; Hwo, S.-Y.; Kirschner, M. W. A protein factor essential for microtubule assembly Proc. Natl. Acad. Sci. U.S.A. 1975, 72, 1858-1862
54. Andreadis, A.; Broderick, J. A.; Kosik, K. S. Relative exon affinities and suboptimal splice site signals lead to non-equivalence of two cassette exons Nucleic Acids Res. 1995, 23, 3585-3593
55. Andreadis, A.; Brown, W. M.; Kosik, K. S. Structure and novel exons of the human tau gene Biochemistry 1992, 31, 10626-10633
56. Buée, L.; Bussière, T.; Buée-Scherrerb, V.; Delacourte, A.; Hof, P. R. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders Brain Res. Rev. 2000, 33, 95-130
57. Levy, S. F.; Leboeuf, A. C.; Massie, M. R.; Jordan, M. A.; Wilson, L.; Feinstein, S. C. Three- and four-repeat tau regulate the dynamic instability of two distinct microtubule subpopulations in qualitatively different manners. Implications for neurodegeneration J. Biol. Chem. 2005, 280, 13520-13528
58. Jeganathan, S.; Hascher, A.; Chinnathambi, S.; Biernat, J.; Mandelkow, E. M.; Mandelkow, E. Proline-directed pseudophosphorylation at AT8 and PHF1 epitopes induces a compaction of the paperclip folding of tau and generates a pathological (MC-1) conformation J. Biol. Chem. 2008, 283, 32066-32076
59. Mukrasch, M. D.; Bibow, S.; Korukottu, J.; Jeganathan, S.; Biernat, J.; Griesinger, C.; Mandelkow, E.; Zweckstetter, M. Structural polymorphism of 441-residue tau at single residue resolution PLoS Biol. 2009, 7, e34
60. von Bergen, M.; Friedhoff, P.; Biernat, J.; Heberle, J.; Mandelkow, E. M.; Mandelkow, E. Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming β structure Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 5129-5134
61. Von Bergen, M.; Barghorn, S.; Li, L.; Marx, A.; Biernat, J.; Mandelkow, E. M.; Mandelkow, E. Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local β-structure J. Biol. Chem. 2001, 276, 48165-48174
62. Martin, L.; Latypova, X.; Terro, F. Post-translational modifications of tau protein: implications for Alzheimers disease Neurochem. Int. 2011, 58, 458-471
63. Iqbal, K.; Gong, C.-X.; Liu, F. Microtubule-associated protein tau as a therapeutic target in Alzheimers disease Expert Opin. Ther. Targets 2014, 18, 307-318
64. Spillantini, M. G.; Goedert, M. Tau pathology and neurodegeneration Lancet Neurol. 2013, 12, 609-622
65. Clavaguera, F.; Grueninger, F.; Tolnay, M. Intercellular transfer of tau aggregates and spreading of tau pathology: implications for therapeutic strategies Neuropharmacology 2014, 76, 9-15
66. Bulic, B.; Pickhardt, M.; Mandelkow, E. Progress and developments in tau aggregation inhibitors for Alzheimer disease J. Med. Chem. 2013, 56, 4135-4155
67. Ramachandran, G.; Udgaonkar, J. B. Mechanistic studies unravel the complexity inherent in tau aggregation leading to Alzheimers disease and the tauopathies Biochemistry 2013, 52, 4107-4126
68. Sevcik, J.; Skrabana, R.; Dvorsky, R.; Csokova, N.; Iqbal, K.; Novak, M. X-ray structure of the PHF core C terminus: insight into the folding of the intrinsically disordered protein tau in Alzheimers disease FEBS Lett. 2007, 581, 5872-5878
69. Skrabana, R.; Dvorsky, R.; Sevcik, J.; Novak, M. Monoclonal antibody MN423 as a stable mold facilitates structure determination of disordered tau protein J. Struct. Biol. 2010, 171, 74-81
70. Janke, C.; Beck, M.; Stahl, T.; Holzer, M.; Brauer, K.; Bigl, V.; Arendt, T. Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders Mol. Brain Res. 1999, 68, 119-128
71. Noble, W.; Hanger, D. P.; Gallo, J.-M. Transgenic mouse models of tauopathy in drug discovery CNS Neurol. Disord.: Drug Targets 2010, 9, 403-428
72. Denk, F.; Wade-Martins, R. Knock-out and transgenic mouse models of tauopathies Neurobiol. Aging 2009, 30, 1-13
73. Roberson, E. D. Mouse models of frontotemporal dementia Ann. Neurol. 2012, 72, 837-849
74. Peeraer, E.; Bottelbergs, A.; Van Kolen, K.; Stancu, I. C.; Vasconcelos, B.; Mahieu, M.; Duytschaever, H.; Ver Donck, L.; Torremans, A.; Sluydts, E.; Van Acker, N.; Kemp, J. A.; Mercken, M.; Brunden, K. R.; Trojanowski, J. Q.; Dewachter, I.; Lee, V. M.; Moechars, D. Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice Neurobiol. Dis. 2015, 73, 83-95
75. Pike, V. W. PET radiotracers: crossing the blood-brain barrier and surviving metabolism Trends Pharmacol. Sci. 2009, 30, 431-440
76. Laruelle, M.; Slifstein, M.; Huang, Y. Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography Mol. Imaging Biol. 2003, 5, 363-375
77. Zhang, L.; Villalobos, A.; Beck, E. M.; Bocan, T.; Chappie, T. A.; Chen, L.; Grimwood, S.; Hech, S. D.; Helal, C. J.; Hou, X.; Humphrey, J. M.; Lu, J.; Skaddan, M. B.; McCarthy, T. J.; Verhoest, P. R.; Wager, T. T.; Zasadny, K. Design and selection parameters to accelerate the discovery of novel central nervous system positron emission tomography (PET) ligands and their application in the development of a novel phosphodiesterase 2A PET ligand J. Med. Chem. 2013, 56, 4568-4579
78. Honer, M.; Gobbi, L.; Martarello, L.; Comley, R. A. Radioligand development for molecular imaging of the central nervous system with positron emission tomography Drug Discovery Today 2014, 19, 1936-1944
79. Patel, S.; Gibson, R. In vivo site-directed radiotracers: a minireview Nucl. Med. Biol. 2008, 35, 805-815
80. Celen, S.; Koole, M.; De Angelis, M.; Sannen, I.; Chitneni, S. K.; Alcazar, J.; Dedeurwaerdere, S.; Moechars, D.; Schmidt, M.; Verbruggen, A.; Langlois, X.; Van Laere, K.; Andrés, J. I.; Bormans, G. Preclinical evaluation of 18F-JNJ41510417 as a radioligand for PET imaging of phosphodiesterase-10A in the brain J. Nucl. Med. 2010, 51, 1584-1591
81. Andrés, J. I.; Alcázar, J.; Cid, J. M.; De Angelis, M.; Iturrino, L.; Langlois, X.; Lavreysen, H.; Trabanco, A. A.; Celen, S.; Bormans, G. Synthesis, evaluation and radiolabeling of new potent positive allosteric modulators of the metabotropic glutamate receptor 2 as potential tracers for positron emission tomography imaging J. Med. Chem. 2012, 55, 8685-8699
82. Clinton, L. K.; Blurton-Jones, M.; Myczek, K.; Trojanowski, J. Q.; La Ferla, F. M. Synergistic interactions between Aβ, tau, and α-synuclein: acceleration of neuropathology and cognitive decline J. Neurosci. 2010, 30, 7281-7289
83. Irwin, D. J.; Lee, V. M.-Y.; Trojanowski, J. Q. Parkinsons disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies Nat. Rev. Neurosci. 2013, 14, 626-636
84. Wegmann, S.; Jung, Y.-J.; Chinnathambi, S.; Mandelkow, E.-M.; Mandelkow, E.; Muller, D. J. Human tau isoforms assemble into ribbon-like fibrils that display polymorphic structure and stability J. Biol. Chem. 2010, 285, 27302-27313
85. Okamura, N.; Suemoto, T.; Furumoto, S.; Suzuki, M.; Shimadzu, H.; Akatsu, H.; Yamamoto, T.; Fujiwara, H.; Nemoto, M.; Maruyama, M.; Arai, H.; Yanai, K.; Sawada, T.; Kudo, Y. Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimers disease J. Neurosci. 2005, 25, 10857-10862
86. Honson, N. S.; Johnson, R. L.; Huang, W.; Inglese, J.; Austin, C. P.; Kuret, J. Differentiating Alzheimer disease-associated aggregates with small molecules Neurobiol. Dis. 2007, 28, 251-260
87. Matsumura, K.; Ono, M.; Hayashi, S.; Kimura, H.; Okamoto, Y.; Ihara, M.; Takahashi, R.; Moric, H.; Saji, H. Phenyldiazenyl benzothiazole derivatives as probes for in vivo imaging of neurofibrillary tangles in Alzheimers disease brains Med. Chem. Commun. 2011, 2, 596-600
88. Matsumura, K.; Ono, M.; Kimura, H.; Ueda, M.; Nakamoto, Y.; Togashi, K.; Okamoto, Y.; Ihara, M.; Takahashi, R.; Saji, H. 18F-Labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimers disease brains ACS Med. Chem. Lett. 2012, 3, 58-62
89. Matsumura, K.; Ono, M.; Yoshimura, M.; Kimura, H.; Watanabe, H.; Okamoto, Y.; Ihara, M.; Takahashi, R.; Saji, H. Synthesis and biological evaluation of novel styryl benzimidazole derivatives as probes for imaging of neurofibrillary tangles in Alzheimers disease Bioorg. Med. Chem. 2013, 21, 3356-3362
90. Harada, R.; Okamura, N.; Furumoto, S.; Yoshikawa, T.; Arai, H.; Yanai, K.; Kudo, Y. Use of a benzimidazole derivative BF-188 in fluorescence multispectral imaging for selective visualization of tau protein fibrils in the Alzheimers disease brain Mol. Imaging Biol. 2014, 16, 19-27
91. Rojo, L. E.; Alzate-Morales, J.; Saavedraa, I. N.; Davies, P.; Maccioni, R. B. Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimers disease J. Alzheimers Dis. 2010, 19, 573-589
92. Riss, P. J.; Brichard, L.; Ferrari, V.; Williamson, D. J.; Fryer, T. D.; Hong, Y. T.; Baron, J.-C.; Aigbirhio, F. I. Radiosynthesis and characterization of astemizole derivatives as lead compounds toward PET imaging of τ-pathology Med. Chem. Commun. 2013, 4, 852-855
93. Shao, X.; Carpenter, G. M.; Desmond, T. J.; Sherman, P.; Quesada, C. A.; Fawaz, M.; Brooks, A. F.; Kilbourn, M. R.; Albin, R. L.; Frey, K. A.; Scott, P. J. H. Evaluation of [11C]N-methyl lansoprazole as a radiopharmaceutical for PET imaging of tau neurofibrillary tangles ACS Med. Chem. Lett. 2012, 3, 936-941
94. Fawaz, M. V.; Brooks, A. F.; Rodnick, M. E.; Carpenter, G. M.; Shao, X.; Desmond, T. J.; Sherman, P.; Quesada, C. A.; Hockley, B. G.; Kilbourn, M. R.; Albin, R. L.; Frey, K. A.; Scott, P. J. H. High affinity radiopharmaceuticals based upon lansoprazole for PET imaging of aggregated tau in Alzheimers disease and progressive supranuclear palsy: synthesis, pre-clinical evaluation and lead selection ACS Chem. Neurosci. 2014, 5, 718-730
95. Ono, M.; Hayashi, S.; Matsumura, K.; Kimura, H.; Okamoto, Y.; Ihara, M.; Takahashi, R.; Mori, H.; Saji, H. Rhodanine and thiohydantoin derivatives for detecting tau pathology in Alzheimers brains ACS Chem. Neurosci. 2011, 2, 269-275
96. Saji, H.; Ono, M.; Seki, I. Radioactive iodine labeled organic compound or salt thereof. International Patent WO2011/108236 A1, 2011.
97. Ballatore, C.; Smith, A. B., III; Lee, V. M.-Y.; Trojanowski, J. Q.; Brunden, K. R. Aminothienopyridazines as imaging probes of tau pathology: a patent evaluation of WO2013090497, 2013.
98. Expert Opin. Ther. Pat. 2014, 24, 355-360.
99. Jones, C.; Glaser, M. E.; Wynn, D.; Nairne, J.; Mokkapati, U. P.; Newington, I. M.; Rangaswamy, C.; Jose, J.; Johansson, S. Heterocyclic compounds as imaging probes of tau pathology. International Patent WO2013/090497, 2013.
100. Bulic, B.; Pickhardt, M.; Khlistunova, I.; Biernat, J.; Mandelkow, E. M.; Mandelkow, E.; Waldmann, H. Rhodanine-based tau aggregation inhibitors in cell models of tauopathy Angew. Chem., Int. Ed. 2007, 46, 9215-9219
101. Ballatore, C.; Brunden, K. R.; Piscitelli, F.; James, M. J.; Crowe, A.; Yao, Y.; Hyde, E.; Trojanowski, J. Q.; Lee, V. M.-Y.; Smith, A. B., III. Discovery of brain-penetrant, orally bioavailable aminothienopyridazine inhibitors of tau aggregation J. Med. Chem. 2010, 53, 3739-3747
102. Crowe, A.; James, M. J.; Lee, V. M.-Y.; Smith, A. B., III; Trojanowski, J. Q.; Ballatore, C.; Brunden, K. R. Aminothienopyridazines and methylene blue affect tau fibrillization via cysteine oxidation J. Biol. Chem. 2013, 288, 11024-11037
103. Gobbi, L.; Knust, H.; Koblet, A. Imidazo[2,1]thiazol-3-one derivatives useful as diagnostic agents for Alzheimers disease. International Patent WO2014/026881 A1, 2014.
104. Taghavi, A.; Nasir, S.; Pickhardt, M.; Heyny-von Hauβen, R.; Mall, G.; Mandelkow, E.; Mandelkow, E.-M.; Schmidt, B. N -Benzylidene-benzohydrazides as novel and selective tau-PHF ligands J. Alzheimers Dis. 2011, 27, 835-843
105. http://clinicaltrials.gov/ct2/show/record/NCT02187627.
106. Altman, M. D.; Fischer, C.; Katz, J. D.; Williams, T. M.; Zhang, X.-F.; Zhou, H. Isotopically labeled biaryl urea compounds useful as tau tracers. International Patent WO 2013/181075 A1, 2013.
107. Kemp, S. J.; Storey, L. J.; Storey, J. M. D.; Rickard, J.; Harrington, C. R.; Wischik, C. M.; Clunas, S.; Heinrich, T. K. Ligands for aggregates tau molecules. International Patent WO 2010/034982 A1, 2010.
108. Boländer, A.; Kieser, D.; Voss, C.; Bauer, S.; Schön, C.; Burgold, S.; Bittner, T.; Hölzer, J.; Heyny-von Haußen, R.; Mall, G.; Goetschy, V.; Czech, C.; Knust, H.; Berger, R.; Herms, J.; Hilger, I.; Schmidt, B. Bis(arylvinyl)pyrazines, -pyrimidines, and -pyridazines as imaging agents for tau fibrils and β-amyloid plaques in Alzheimers disease models J. Med. Chem. 2012, 55, 9170-9180
109. Barrio, J. R.; Huang, S. C.; Cole, G.; Satyamurthy, N.; Petric, A.; Phelps, M. E.; Small, G. PET imaging of tangles and plaques in Alzheimer disease with a highly hydrophobic probe J. Labelled Compd. Radiopharm. 1999, 42, S194-195
110. Small, G. W.; Kepe, V.; Ercoli, L. M.; Siddarth, P.; Bookheimer, S. Y.; Miller, K. J.; Lavretsky, H.; Burggren, A. C.; Cole, G. M.; Vinters, H. V.; Thompson, P. M.; Huang, S.-C.; Satyamurthy, N.; Phelps, M. E.; Barrio, J. R. PET of brain amyloid and tau in mild cognitive impairment N. Engl. J. Med. 2006, 355, 2652-2663
111. Shin, J.; Kepe, V.; Barrio, J. R.; Small, G. W. The merits of FDDNP-PET imaging in Alzheimers disease J. Alzheimers Dis. 2011, 26, 135-145
112. Nelson, L. D.; Siddarth, P.; Kepe, V.; Scheibel, K. E.; Huang, S.-C.; Barrio, J. R.; Small, G. W. Positron emission tomography of brain beta-amyloid and tau levels in adults with Down syndrome Arch. Neurol. 2011, 68, 768-774
113. Small, G. W.; Kepe, V.; Siddarth, P.; Ercoli, L. M.; Merrill, D. A.; Donoghue, N.; Bookheimer, S. Y.; Martinez, J.; Omalu, B.; Bailes, J.; Barrio, J. R. PET scanning of brain tau in retired National Football League players: preliminary findings Am. J. Geriatr. Psychiatry 2013, 21, 138-44
114. Thompson, P. W.; Ye, L.; Morgenstern, J. L.; Sue, L.; Beach, T. G.; Judd, D. J.; Shipley, N. J.; Libri, V.; Lockhart, A. Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimers disease pathologies J. Neurochem. 2009, 109, 623-630
115. Fodero-Tavoletti, M. T.; Okamura, N.; Furumoto, S.; Mulligan, R. S.; Connor, A. R.; McLean, C. A.; Cao, D.; Rigopoulos, A.; Cartwright, G. A.; OKeefe, G.; Gong, S.; Adlard, P. A.; Barnham, K. J.; Rowe, C. C.; Masters, C. L.; Kudo, Y.; Cappai, R.; Yanai, K.; Villemagne, V. L. 18F-THK-523: a novel in vivo tau imaging ligand for Alzheimers disease Brain 2011, 134, 1089-1100
116. Okamura, N.; Furumuto, S.; Harada, R.; Tago, T.; Yoshikawa, T.; Fodero-Tavoletti, M.; Mulligan, R. S.; Villemagne, V. L.; Akatsu, H.; Yamamoto, T.; Arai, H.; Iwata, R.; Yanai, K.; Kudo, Y. Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease J. Nucl. Med. 2013, 54, 1420-1427
117. Villemagne, V. L.; Furumoto, S.; Fodero-Tavoletti, M. T.; Mulligan, R. S.; Hodges, J.; Harada, R.; Yates, P.; Piguet, O.; Pejoska, S.; Doré, V.; Yanai, K.; Masters, C. L.; Kudo, Y.; Rowe, C. C.; Okamura, N. In vivo evaluation of a novel tau imaging tracer for Alzheimers disease Eur. J. Nucl. Med. Mol. Imaging 2014, 41, 816-826
118. Okamura, N.; Furumoto, S.; Fodero-Tavoletti, M. T.; Mulligan, R. S.; Harada, R.; Yates, P.; Pejoska, S.; Kudo, Y.; Masters, C. L.; Yanai, K.; Rowe, C. C.; Villemagne, V. L. Non-invasive assessment of Alzheimers disease neurofibrillary pathology using 18F-THK5105 PET Brain 2014, 137, 1762-1771
119. Bakhti, M.; Aggarwal, S.; Simons, M. Myelin architecture: zippering membranes tightly together Cell. Mol. Life Sci. 2014, 71, 1265-1277
120. Tago, T.; Furumoto, S.; Okamura, N.; Harada, R.; Ishikawa, Y.; Arai, H.; Yanai, K.; Iwata, R.; Kudo, Y. Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging J. Labelled Compd. Radiopharm. 2014, 57, 18-24
121. Okamura, N.; Furumoto, S.; Harada, R.; Tago, T.; Iwata, R.; Tashiro, M.; Furukawa, K.; Arai, H.; Yanai, K.; Kudo, Y. Characterization of 18F-THK-5351, a novel PET tracer for imaging tau pathology in Alzheimers disease Eur. J. Nucl. Med. Mol. Imaging 2014, 41, S260
122. Maruyama, M.; Shimada, H.; Suhara, T.; Shinotoh, H.; Ji, B.; Maeda, J.; Zhang, M.-R.; Trojanowski, J. Q.; Lee, V. M.-Y.; Ono, M.; Masamoto, K.; Takano, H.; Sahara, N.; Iwata, N.; Okamura, N.; Furumoto, S.; Kudo, Y.; Chang, Q.; Saido, T. C.; Takashima, A.; Lewis, J.; Jang, M.-K.; Aoki, I.; Ito, H.; Higuchi, M. Imaging of tau pathology in mouse model and in Alzheimer patients compared to normal controls Neuron 2013, 79, 1-15
123. Hashimoto, H.; Kawamura, K.; Igarashi, N.; Takei, M.; Fujishiro, T.; Aihara, Y.; Shiomi, S.; Muto, M.; Ito, T.; Furutsuka, K.; Yamasaki, T.; Yui, J.; Xie, L.; Ono, M.; Hatori, A.; Nemoto, K.; Suhara, T.; Higuchi, M.; Zhang, M.-R. Radiosynthesis, photoisomerization, biodistribution, and metabolite analysis of 11C-PBB3 as a clinically useful PET probe for imaging of tau pathology J. Nucl. Med. 2014, 55, 1532-1538
124. Lei, Y.; Yu, L.; Zhou, B.; Zhu, C.; Wen, Z.; Lin, S. H. Landscapes of four-enantiomer conical intersections for photoisomerization of stilbene: CASSCF calculation J. Phys. Chem. A 2014, 118, 9021-903
125. Waldeck, D. H. Photoisomerization dynamics of stilbene Chem. Rev. 1991, 91, 415-436
126. Szardenings, A. K.; Kolb, H. C.; Walsh, J. C.; Chen, G.; Gangadharmath, U. B.; Kasi, D.; Liu, C.; Sinha, A.; Wang, E.; Yu, C.; Zhang, W.; Chen, K.; Mocharla, V. P.; Scott, P. J. H. Imaging agents for detecting neurological dysfunction. International Patent US 2012/0302755 A1, 2012.
127. Cashion, D. K.; Cheng, G.; Kasi, D.; Kolb, H. C. Imaging agents for detecting neurological disorders. International Patent WO 2011/119565 A1, 2011.
128. Zhang, W.; Arteaga, J.; Cashion, D. K.; Chen, G.; Gangadharmath, U.; Gomez, L. F.; Kasi, D.; Lam, C.; Liang, Q.; Liu, C.; Mocharla, V. P.; Mu, F.; Sinha, A.; Szardenings, A. K.; Wang, E.; Walsh, J. C.; Xia, C.; Yu, C.; Zhao, T.; Kolb, H. C. A highly selective and specific PET tracer for imaging of tau pathologies J. Alzheimers Dis. 2012, 31, 601-612
129. Xia, C.-F.; Arteaga, J.; Chen, G.; Gangadharmath, U.; Gomez, L. F.; Kasi, D.; Lam, C.; Liang, Q.; Liu, C.; Mocharla, V. P.; Mu, F.; Sinha, A.; Su, H.; Szardenings, A. K.; Walsh, J. C.; Wang, E.; Yu, C.; Zhang, W.; Zhao, T.; Kolb, H. C. [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimers disease Alzheimers Dementia 2013, 9, 666-676
130. Radde, R.; Bolmont, T.; Kaeser, S. A.; Coomaraswamy, J.; Lindau, D.; Stoltze, L.; Calhoun, M. E.; Jaeggi, F.; Wolburg, H.; Gengler, S.; Haass, C.; Ghetti, B.; Czech, C.; Hoelscher, C.; Mathews, P. M.; Jucker, M. Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology EMBO Rep. 2006, 7, 940-946
131. Chien, D. T.; Bahri, S.; Szardenings, A. K.; Walsh, J. C.; Mu, F.; Su, M.-Y.; Shankle, W. R.; Elizarov, A.; Kolb, H. C. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807 J. Alzheimers Dis. 2013, 34, 457-468
132. Mintun, M.; Schwarz, A.; Joshi, A.; Shcherbinin, S.; Chien, D.; Elizarov, A.; Su, M.-Y.; Shankle, W.; Pontecorvo, M.; Tauscher, J.; Skovronsky, D.; Kolb, H. C. Exploratory analyses of regional human brain distribution of the PET tau tracer F18-labeled T807 (AV-1541) in subjects with normal cognitive function or cognitive impairment thought to be due to AD Alzheimers Dementia 2013, 9, P842
133. Kolb, H. C. Human amyloid imaging conference, 2013, www.alzforum.org/news/conference-coverage/hai-spotlight-tau-tracers-human-amyloid-imaging-meeting.
134. Chien, D. T.; Katrin, A.; Bahri, S.; Walsh, J. C.; Mu, F.; Xia, C.; Shankle, W. R.; Lerner, A. J.; Su, M.-Y.; Elizarov, A.; Kolb, H. C. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808 J. Alzheimers Dis. 2014, 38, 171-184
135. Kolb, H. C.; Attardo, G.; Mintun, M.; Chien, D.; Elizarov, A.; Conti, P.; Miller, C.; Joshi, A.; Skovronsky, D. First case report: image to autopsy correlation for tau imaging with [18F]-T808 (AV-680) Alzheimers Dementia 2013, 9, P844-845
136. Landau, M.; Sawaya, M. R.; Faull, K. F.; Laganowsky, A.; Jiang, L.; Sievers, S. A.; Liu, J.; Barrio, J. R.; Eisenberg, D. Towards a pharmacophore for amyloid PLoS Biol. 2011, 9, e1001080