The development and validation of tau PET tracers: current status and future directions

Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259

Morris JC, Price JL (2001) Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer’s disease. J Mol Neurosci 17:101–118

Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E et al (2015) Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol. 11:457–470. https://doi.org/10.1038/nrneurol.2015.119

Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185

Villemagne VL, Dore V, Burnham SC, Masters CL, Rowe CC (2018) Imaging tau and amyloid-beta proteinopathies in Alzheimer disease and other conditions. Nat Rev Neurol 14:225–236. https://doi.org/10.1038/nrneurol.2018.9

Goedert M, Crowther RA, Garner CC (1991) Molecular characterization of microtubule-associated proteins tau and MAP2. Trends Neurosci 14:193–199

Villemagne VL, Fodero-Tavoletti MT, Masters CL, Rowe CC (2015) Tau imaging: early progress and future directions. Lancet Neurol 14:114–124. https://doi.org/10.1016/S1474-4422(14)70252-2

Harada R, Okamura N, Furumoto S, Tago T, Yanai K, Arai H et al (2016) Characteristics of tau and its ligands in PET imaging. Biomolecules 6:7. https://doi.org/10.3390/biom6010007

Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS et al (2013) Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12:207–216. https://doi.org/10.1016/S1474-4422(12)70291-0

Perrin RJ, Fagan AM, Holtzman DM (2009) Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature 461:916–922. https://doi.org/10.1038/nature08538

Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I et al (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755–766. https://doi.org/10.1007/s00401-014-1349-0

Scholl M, Lockhart SN, Schonhaut DR, O’Neil JP, Janabi M, Ossenkoppele R et al (2016) PET imaging of tau deposition in the aging human brain. Neuron 89:971–982. https://doi.org/10.1016/j.neuron.2016.01.02813

Rabinovici GD, Jagust WJ (2009) Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo. Behav Neurol 21:117–128. https://doi.org/10.3233/BEN-2009-0232

Schwarz AJ, Shcherbinin S, Slieker LJ, Risacher SL, Charil A, Irizarry MC et al (2018) Topographic staging of tau positron emission tomography images. Alzheimers Dement (Amst) 10:221–231. https://doi.org/10.1016/j.dadm.2018.01.006

Giacobini E, Gold G (2013) Alzheimer disease therapy–moving from amyloid-beta to tau. Nat Rev Neurol 9:677–686. https://doi.org/10.1038/nrneurol.2013.223

DeKosky ST, Blennow K, Ikonomovic MD, Gandy S (2013) Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nat Rev Neurol 9:192–200. https://doi.org/10.1038/nrneurol.2013.36

Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Harada R, Mulligan RS, Kudo Y et al (2012) The challenges of tau imaging. Future Neurol 7:409–421. https://doi.org/10.2217/fnl.12.34

Furumoto S, Tago T, Harada R, Kudo Y, Okamura N (2017) 18F-Labeled 2-arylquinoline derivatives for tau imaging: chemical, radiochemical, biological and clinical features. Curr Alzheimer Res 14:178–185

Okamura N, Harada R, Furumoto S, Arai H, Yanai K, Kudo Y (2014) Tau PET imaging in Alzheimer’s disease. Curr Neurol Neurosci Rep 14:500. https://doi.org/10.1007/s11910-014-0500-6

Okamura N, Suemoto T, Furumoto S, Suzuki M, Shimadzu H, Akatsu H et al (2005) Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimer’s disease. J Neurosci 25:10857–10862. https://doi.org/10.1523/JNEUROSCI.1738-05.2005

Harada R, Okamura N, Furumoto S, Tago T, Maruyama M, Higuchi M et al (2013) Comparison of the binding characteristics of [18F]THK-523 and other amyloid imaging tracers to Alzheimer’s disease pathology. Eur J Nucl Med Mol Imaging 40:125–132. https://doi.org/10.1007/s00259-012-2261-2

Fodero-Tavoletti MT, Okamura N, Furumoto S, Mulligan RS, Connor AR, McLean CA et al (2011) 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer’s disease. Brain 134:1089–1100. https://doi.org/10.1093/brain/awr038

Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Hodges J, Harada R et al (2014) In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease. Eur J Nucl Med Mol Imaging 41:816–826. https://doi.org/10.1007/s00259-013-2681-7

Okamura N, Furumoto S, Harada R, Tago T, Yoshikawa T, Fodero-Tavoletti M et al (2013) Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. J Nucl Med 54:1420–1427. https://doi.org/10.2967/jnumed.112.117341

Okamura N, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Harada R, Yates P et al (2014) Non-invasive assessment of Alzheimer’s disease neurofibrillary pathology using 18F-THK5105 PET. Brain 137:1762–1771. https://doi.org/10.1093/brain/awu064

Li Y, Tsui W, Rusinek H, Butler T, Mosconi L, Pirraglia E et al (2015) Cortical laminar binding of PET amyloid and tau tracers in Alzheimer disease. J Nucl Med 56:270–273. https://doi.org/10.2967/jnumed.114.149229

Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N et al (2015) [18F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 42:1052–1061. https://doi.org/10.1007/s00259-015-3035-4

Ishiki A, Okamura N, Furukawa K, Furumoto S, Harada R, Tomita N et al (2015) Longitudinal assessment of tau pathology in patients with Alzheimer’s disease using [18F]THK-5117 positron emission tomography. PLoS One 10:e0140311. https://doi.org/10.1371/journal.pone.0140311

Tago T, Furumoto S, Okamura N, Harada R, Adachi H, Ishikawa Y et al (2016) Preclinical evaluation of [18F]THK-5105 enantiomers: effects of chirality on its effectiveness as a tau imaging radiotracer. Mol Imaging Biol 18:258–266. https://doi.org/10.1007/s11307-015-0879-8

Tago T, Furumoto S, Okamura N, Harada R, Adachi H, Ishikawa Y et al (2016) Structure-activity relationship of 2-Arylquinolines as PET imaging tracers for tau pathology in Alzheimer disease. J Nucl Med 57:608–614. https://doi.org/10.2967/jnumed.115.166652

Chiotis K, Saint-Aubert L, Savitcheva I, Jelic V, Andersen P, Jonasson M et al (2016) Imaging in vivo tau pathology in Alzheimer’s disease with THK5317 PET in a multimodal paradigm. Eur J Nucl Med Mol Imaging 43:1686–1699. https://doi.org/10.1007/s00259-016-3363-z

Saint-Aubert L, Almkvist O, Chiotis K, Almeida R, Wall A, Nordberg A (2016) Regional tau deposition measured by [18F]THK5317 positron emission tomography is associated to cognition via glucose metabolism in Alzheimer’s disease. Alzheimer’s Res Ther 8:38. https://doi.org/10.1186/s13195-016-0204-z

Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N et al (2016) 18F-THK5351: a novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer’s disease. J Nucl Med 57:208–214. https://doi.org/10.2967/jnumed.115.164848

Betthauser TJ, Lao PJ, Murali D, Barnhart TE, Furumoto S, Okamura N et al (2017) In vivo comparison of tau radioligands 18F-THK-5351 and 18F-THK-5317. J Nucl Med 58:996–1002. https://doi.org/10.2967/jnumed.116.182980

Kang JM, Lee SY, Seo S, Jeong HJ, Woo SH, Lee H et al (2017) Tau positron emission tomography using [18F]THK5351 and cerebral glucose hypometabolism in Alzheimer’s disease. Neurobiol Aging 59:210–219. https://doi.org/10.1016/j.neurobiolaging.2017.08.008

Sone D, Imabayashi E, Maikusa N, Okamura N, Furumoto S, Kudo Y et al (2017) Regional tau deposition and subregion atrophy of medial temporal structures in early Alzheimer’s disease: a combined positron emission tomography/magnetic resonance imaging study. Alzheimers Dement (Amst) 9:35–40. https://doi.org/10.1016/j.dadm.2017.07.001

Ishiki A, Harada R, Okamura N, Tomita N, Rowe CC, Villemagne VL et al (2017) Tau imaging with [18F]THK-5351 in progressive supranuclear palsy. Eur J Neurol 24:130–136. https://doi.org/10.1111/ene.13164

Shimizu S, Imabayashi E, Takenoshita N, Okamura N, Furumoto S, Kudo Y et al (2018) Case of progressive supranuclear palsy detected by tau imaging with [18F]THK-5351 before the appearance of characteristic clinical features. Geriatr Gerontol Int 18:501–502. https://doi.org/10.1111/ggi.13229

Brendel M, Schonecker S, Hoglinger G, Lindner S, Havla J, Blautzik J et al (2017) [18F]-THK5351 PET correlates with topology and symptom severity in progressive supranuclear palsy. Front Aging Neurosci 9:440. https://doi.org/10.3389/fnagi.2017.00440

Kikuchi A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y et al (2016) In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET. Neurology 87:2309–2316. https://doi.org/10.1212/WNL.0000000000003375

Harada R, Ishiki A, Kai H, Sato N, Furukawa K, Furumoto S et al (2018) Correlations of 18F-THK5351 PET with postmortem burden of tau and astrogliosis in Alzheimer disease. J Nucl Med 59:671–674. https://doi.org/10.2967/jnumed.117.197426

Lee H, Seo S, Lee SY, Jeong HJ, Woo SH, Lee KM et al (2018) [18F]-THK5351 PET imaging in patients with semantic variant primary progressive aphasia. Alzheimer Dis Assoc Disord 32:62–69. https://doi.org/10.1097/WAD.0000000000000216

Takaya M, Ishii K, Hosokawa C, Saigoh K, Shirakawa O (2018) Tau accumulation in two patients with frontotemporal lobe degeneration showing different types of aphasia using 18F-THK-5351 positron emission tomography: a case report. Int Psychogeriatr 30:641–646. https://doi.org/10.1017/S1041610217002277

Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J et al (2013) Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79:1094–1108. https://doi.org/10.1016/j.neuron.2013.07.037

Ono M, Sahara N, Kumata K, Ji B, Ni R, Koga S 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

Shimada H, Kitamura S, Shinotoh H, Endo H, Niwa F, Hirano S et al (2017) Association between Abeta and tau accumulations and their influence on clinical features in aging and Alzheimer’s disease spectrum brains: a [11C]PBB3-PET study. Alzheimers Dement (Amst) 6:11–20. https://doi.org/10.1016/j.dadm.2016.12.009

Perez-Soriano A, Arena JE, Dinelle K, Miao Q, McKenzie J, Neilson N 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

Chiotis K, Stenkrona P, Almkvist O, Stepanov V, Ferreira D, Arakawa R et al (2018) Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain. Eur J Nucl Med Mol Imaging. https://doi.org/10.1007/s00259-018-4012-5

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

Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY et al (2013) Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis 34:457–468. https://doi.org/10.3233/JAD-122059

Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu FR, Xia CF et al (2014) Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimers Dis 38:171–184. https://doi.org/10.3233/JAD-130098

Marquie M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA, Rycyna LG 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

Marquie M, Siao Tick Chong M, Anton-Fernandez A, Verwer EE, Saez-Calveras N, Meltzer AC et al (2017) [F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging. Acta Neuropathol 134:619–628. https://doi.org/10.1007/s00401-017-1740-8

Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D et al (2016) Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol 79:110–119. https://doi.org/10.1002/ana.24546

Schwarz AJ, Yu P, Miller BB, Shcherbinin S, Dickson J, Navitsky M et al (2016) Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages. Brain 139:1539–1550. https://doi.org/10.1093/brain/aww023

Devous MD Sr, Joshi AD, Navitsky M, Southekal S, Pontecorvo MJ, Shen H et al (2017) Test-retest reproducibility for the tau PET imaging agent Flortaucipir F 18. J Nucl Med. https://doi.org/10.2967/jnumed.117.200691

Sperling R, Mormino E, Johnson K (2014) The evolution of preclinical Alzheimer’s disease: implications for prevention trials. Neuron 84:608–622. https://doi.org/10.1016/j.neuron.2014.10.038

Pontecorvo MJ, Devous MD Sr, Navitsky M, Lu M, Salloway S, Schaerf FW et al (2017) Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain 140:748–763. https://doi.org/10.1093/brain/aww334

Okamura N, Yanai K (2017) Brain imaging: applications of tau PET imaging. Nat Rev Neurol 13:197–198. https://doi.org/10.1038/nrneurol.2017.38

Scholl M, Ossenkoppele R, Strandberg O, Palmqvist S, Fs Swedish Bio, Jogi J et al (2017) Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer’s disease. Brain 140:2286–2294. https://doi.org/10.1093/brain/awx171

Ossenkoppele R, Schonhaut DR, Scholl M, Lockhart SN, Ayakta N, Baker SL et al (2016) Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease. Brain 139:1551–1567. https://doi.org/10.1093/brain/aww027

Nasrallah IM, Chen YJ, Hsieh MK, Phillips JS, Ternes K, Stockbower GE et al (2018) 18F-Flortaucipir PET/MRI correlations in nonamnestic and amnestic variants of Alzheimer disease. J Nucl Med 59:299–306. https://doi.org/10.2967/jnumed.117.194282

Ossenkoppele R, Schonhaut DR, Baker SL, O’Neil JP, Janabi M, Ghosh PM et al (2015) Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy. Ann Neurol 77:338–342. https://doi.org/10.1002/ana.24321

Gomperts SN, Locascio JJ, Makaretz SJ, Schultz A, Caso C, Vasdev N et al (2016) Tau positron emission tomographic imaging in the Lewy body diseases. JAMA Neurol 73:1334–1341. https://doi.org/10.1001/jamaneurol.2016.3338

Kantarci K, Lowe VJ, Boeve BF, Senjem ML, Tosakulwong N, Lesnick TG et al (2017) AV-1451 tau and beta-amyloid positron emission tomography imaging in dementia with Lewy bodies. Ann Neurol 81:58–67. https://doi.org/10.1002/ana.24825

Gordon BA, Friedrichsen K, Brier M, Blazey T, Su Y, Christensen J et al (2016) The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging. Brain 139:2249–2260. https://doi.org/10.1093/brain/aww139

Chhatwal JP, Schultz AP, Marshall GA, Boot B, Gomez-Isla T, Dumurgier J et al (2016) Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly. Neurology 87:920–926. https://doi.org/10.1212/WNL.0000000000003050

Mattsson N, Scholl M, Strandberg O, Smith R, Palmqvist S, Insel PS et al (2017) 18F-AV-1451 and CSF T-tau and P-tau as biomarkers in Alzheimer’s disease. EMBO Mol Med. 9:1212–1223. https://doi.org/10.15252/emmm.201707809

Hammes J, Bischof GN, Giehl K, Faber J, Drzezga A, Klockgether T et al (2017) Elevated in vivo [18F]-AV-1451 uptake in a patient with progressive supranuclear palsy. Mov Disord 32:170–171. https://doi.org/10.1002/mds.26727

Smith R, Schain M, Nilsson C, Strandberg O, Olsson T, Hagerstrom D et al (2017) Increased basal ganglia binding of 18F-AV-1451 in patients with progressive supranuclear palsy. Mov Disord 32:108–114. https://doi.org/10.1002/mds.26813

Cho H, Choi JY, Hwang MS, Lee SH, Ryu YH, Lee MS et al (2017) Subcortical 18F-AV-1451 binding patterns in progressive supranuclear palsy. Mov Disord 32:134–140. https://doi.org/10.1002/mds.26844

Schonhaut DR, McMillan CT, Spina S, Dickerson BC, Siderowf A, Devous MD Sr et al (2017) 18F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: a multicenter study. Ann Neurol 82:622–634. https://doi.org/10.1002/ana.25060

Marquie M, Normandin MD, Meltzer AC, Siao Tick Chong M, Andrea NV, Anton-Fernandez A et al (2017) Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies. Ann Neurol 81:117–128. https://doi.org/10.1002/ana.24844

Lowe VJ, Curran G, Fang P, Liesinger AM, Josephs KA, Parisi JE 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

Sander K, Lashley T, Gami P, Gendron T, Lythgoe MF, Rohrer JD 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. Alzheimers Dement 12:1116–1124. https://doi.org/10.1016/j.jalz.2016.01.003

Smith R, Scholl M, Widner H, van Westen D, Svenningsson P, Hagerstrom D et al (2017) In vivo retention of 18F-AV-1451 in corticobasal syndrome. Neurology 89:845–853. https://doi.org/10.1212/WNL.0000000000004264

Cho H, Baek MS, Choi JY, Lee SH, Kim JS, Ryu YH et al (2017) 18F-AV-1451 binds to motor-related subcortical gray and white matter in corticobasal syndrome. Neurology 89:1170–1178. https://doi.org/10.1212/WNL.0000000000004364

Josephs KA, Whitwell JL, Tacik P, Duffy JR, Senjem ML, Tosakulwong N et al (2016) [18F]AV-1451 tau-PET uptake does correlate with quantitatively measured 4R-tau burden in autopsy-confirmed corticobasal degeneration. Acta Neuropathol 132:931–933. https://doi.org/10.1007/s00401-016-1618-1

McMillan CT, Irwin DJ, Nasrallah I, Phillips JS, Spindler M, Rascovsky K et al (2016) Multimodal evaluation demonstrates in vivo 18F-AV-1451 uptake in autopsy-confirmed corticobasal degeneration. Acta Neuropathol 132:935–937. https://doi.org/10.1007/s00401-016-1640-3

Hansen AK, Knudsen K, Lillethorup TP, Landau AM, Parbo P, Fedorova T et al (2016) In vivo imaging of neuromelanin in Parkinson’s disease using 18F-AV-1451 PET. Brain 139:2039–2049. https://doi.org/10.1093/brain/aww098

Coakeley S, Cho SS, Koshimori Y, Rusjan P, Ghadery C, Kim J et al (2018) [18F]AV-1451 binding to neuromelanin in the substantia nigra in PD and PSP. Brain Struct Funct 223:589–595. https://doi.org/10.1007/s00429-017-1507-y

Laterra J, Keep R, Betz LA, Goldstein GW (1999) Blood-cerebrospinal fluid barrier. Basic neurochemistry: molecular, cellular and medical aspects, 6th edn. Lippincott-Raven, Philadelphia

Ikonomovic MD, Abrahamson EE, Price JC, Mathis CA, Klunk WE (2016) [F-18]AV-1451 positron emission tomography retention in choroid plexus: more than “off-target” binding. Ann Neurol 80:307–308. https://doi.org/10.1002/ana.24706

Choi JY, Cho H, Ahn SJ, Lee JH, Ryu YH, Lee MS et al (2018) Off-Target 18F-AV-1451 binding in the basal ganglia correlates with age-related iron accumulation. J Nucl Med 59:117–120. https://doi.org/10.2967/jnumed.117.195248

Hostetler ED, Walji AM, Zeng Z, Miller P, Bennacef I, Salinas C 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

Vermeiren C, Motte P, Viot D, Mairet-Coello G, Courade JP, Citron M 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

Hansen AK, Brooks DJ, Borghammer P (2018) MAO-B inhibitors do not block in vivo flortaucipir ([18F]-AV-1451) binding. Mol Imaging Biol 20:356–360. https://doi.org/10.1007/s11307-017-1143-1

Smith R, Scholl M, Londos E, Ohlsson T, Hansson O (2018) 18F-AV-1451 in Parkinson’s disease with and without dementia and in dementia with Lewy bodies. Sci Rep 8:4717. https://doi.org/10.1038/s41598-018-23041-x

Bevan-Jones WR, Cope TE, Jones PS, Passamonti L, Hong YT, Fryer TD et al (2017) [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. https://doi.org/10.1136/jnnp-2017-316402

Jang YK, Lyoo CH, Park S, Oh SJ, Cho H, Oh M et al (2018) Head to head comparison of [18F] AV-1451 and [18F] THK5351 for tau imaging in Alzheimer’s disease and frontotemporal dementia. Eur J Nucl Med Mol Imaging 45:432–442. https://doi.org/10.1007/s00259-017-3876-0

Ishiki A, Harada R, Kai H, Sato N, Totsune T, Tomita N et al (2018) Neuroimaging-pathological correlations of [18F]THK5351 PET in progressive supranuclear palsy. Acta Neuropathol Commun 6:53. https://doi.org/10.1186/s40478-018-0556-7

Ng KP, Pascoal TA, Mathotaarachchi S, Therriault J, Kang MS, Shin M et al (2017) Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain. Alzheimer’s Res Ther 9:25. https://doi.org/10.1186/s13195-017-0253-y

Lemoine L, Gillberg PG, Svedberg M, Stepanov V, Jia Z, Huang J et al (2017) Comparative binding properties of the tau PET tracers THK5117, THK5351, PBB3, and T807 in postmortem Alzheimer brains. Alzheimer’s Res Ther 9:96. https://doi.org/10.1186/s13195-017-0325-z

Ishibashi K, Kameyama M, Tago T, Toyohara J, Ishii K (2017) Potential use of 18F-THK5351 PET to identify Wallerian degeneration of the pyramidal tract caused by cerebral infarction. Clin Nucl Med 42:e523–e524. https://doi.org/10.1097/RLU.0000000000001868

Honer M, Gobbi L, Knust H, Kuwabara H, Muri D, Koerner M et al (2018) Preclinical evaluation of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 as novel PET radiotracers for imaging tau aggregates in Alzheimer disease. J Nucl Med 59:675–681. https://doi.org/10.2967/jnumed.117.196741

Gobbi LC, Knust H, Korner M, Honer M, Czech C, Belli S et al (2017) Identification of three novel radiotracers for imaging aggregated tau in Alzheimer’s disease with positron emission tomography. J Med Chem 60:7350–7370. https://doi.org/10.1021/acs.jmedchem.7b00632

Wong DF, Comley R, Kuwabara H, Rosenberg PB, Resnick SM, Ostrowitzki S et al (2018) First in-human PET study of 3 novel tau radiopharmaceuticals: [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948. J Nucl Med. https://doi.org/10.2967/jnumed.118.209916

Bohorquez S, Barret O, Tamagnan G, Alagille D, Marik J, Ayalon G et al (2016) Evaluation of tau burden in a cross-sectional cohort of Alzheimer’s disease subjects using [18F]GTP1 (Genentech Tau Probe 1). Alzheimer’s Dementia. https://doi.org/10.1016/j.jalz.2016.07.096

Walji AM, Hostetler ED, Selnick H, Zeng Z, Miller P, Bennacef I et al (2016) Discovery of 6-(Fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F]-MK-6240): a positron emission tomography (PET) imaging agent for quantification of neurofibrillary tangles (NFTs). J Med Chem 59:4778–4789. https://doi.org/10.1021/acs.jmedchem.6b00166

Betthauser TJ, Cody KA, Zammit MD, Murali D, Converse AK, Barnhart TE et al (2018) In vivo characterization and quantification of neurofibrillary tau PET radioligand [18F]MK-6240 in humans from Alzheimer’s disease dementia to young controls. J Nucl Med. https://doi.org/10.2967/jnumed.118.209650

Barret O, Seibyl J, Stephans A, Madonia J, Alagille D, Mueller A et al (2017) First in human characterization of PI-2620, a next generation PET tracer for assessing tau in AD and other tauopathies. AD/PD 2017 Poster Presentation.  https://www.acimmune.com/en/ad-pd-2017/ . Accessed 28 June 2018 

Stephans A (2017) Characterization of novel PET tracer for the assessment of tau pathology in Alzheimer’s disease and other tauopathies. AD/PD 2017 Oral Presentation.  https://www.acimmune.com/en/ad-pd-2017/ . Accessed 28 June 2018