Head to head comparison of [18F] AV-1451 and [18F] THK5351 for tau imaging in Alzheimer’s disease and frontotemporal dementia
Tau accumulation is a core pathologic change in various neurodegenerative diseases including Alzheimer’s disease and frontotemporal lobar degeneration-tau. Recently, tau positron emission tomography tracers such as [18F] AV-1451 and [18F] THK5351 have been developed to detect tau deposition in vivo. In the present study, we performed a head to head comparison of these two tracers in Alzheimer’s disease and frontotemporal dementia cases and aimed to investigate which tracers are better suited to image tau in these disorders.
A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We recruited eight participants (two Alzheimer’s disease, four frontotemporal dementia and two normal controls) who underwent magnetic resonance image, amyloid positron emission tomography with [18F]-Florbetaben and tau positron emission tomography with both THK5351 and AV-1451. To measure regional AV1451 and THK5351 uptakes, we used the standardized uptake value ratios by dividing mean activity in target volume of interest by mean activity in the cerebellar hemispheric gray matter.
Although THK5351 and AV-1451 uptakes were highly correlated, cortical uptake of AV-1451 was more striking in Alzheimer’s disease, while cortical uptake of THK5351 was more prominent in frontotemporal dementia. THK5351 showed higher off-target binding than AV-1451 in the white matter, midbrain, thalamus, and basal ganglia.
AV-1451 is more sensitive and specific to Alzheimer’s disease type tau and shows lower off-target binding, while THK5351 may mirror non-specific neurodegeneration.
KeywordsTau Av-1451 THK5351 Alzheimer’s disease Frontotemporal dementia
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2768); and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. NRF-2017R1A2B2005081).
Compliance with ethical standards
Conflict of interest
G.D.R. receives research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare and Piramal. He has received consulting fees and speaking honoraria from Eisai, Genentech, Roche, Lundbeck, Putnam and Merck.
Role of the funder
The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 4.Rascovsky K, Hodges J, Knopman D, Mendez M, Kramer J, Neuhaus J, et al. Can clinical features predict tau pathology in patients with behavioral variant frontotemporal dementia? Annual meeting of the American-Academy-of-Neurology. 2013.Google Scholar
- 8.Okamura N, Furumoto S, Furukawa K, Ishiki A, Harada R, Iwata R, et al. PET imaging of tau pathology in mild cognitive impairment and Alzheimer’s disease with [18F]THK-5351. Annual meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging. 2015.Google Scholar
- 9.Ishiki A, Harada R, Okamura N, Tomita N, Rowe CC, Villemagne VL, et al. Tau imaging with [18 F]THK-5351 in progressive supranuclear palsy. Eur J Neurol. 2016.Google Scholar
- 19.Ng KP, Massarweh G, Soucy JP, Gravel P, Pascoal TA, Mathotaarachchi S, et al. Selegiline reduces brain [18F]THK5351 binding. 11th Human Amyloid Imaging. 2017;187.Google Scholar
- 21.McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Barthel H, Luthardt J, Becker G, Patt M, Hammerstein E, Hartwig K, et al. Individualized quantification of brain beta-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer’s disease and healthy controls. Eur J Nucl Med Mol Imaging. 2011;38:1702–14.CrossRefPubMedGoogle Scholar
- 27.Collins DL, Zijdenbos AP, Baaré WFC, Evans AC. ANIMAL+INSECT: Improved cortical structure segmentation. In: Kuba A, Šáamal M, Todd-Pokropek A, editors. Information processing in medical imaging: 16th international conference, IPMI’99 Visegrád, Hungary, June 28 – July 2, 1999 Proceedings. Berlin, Heidelberg: Springer Berlin Heidelberg; 1999. p. 210–23.Google Scholar
- 28.Martersteck A, Sridhar J, Rainford A, Mesulam M, Rogalski E. Recovering signal from AV1451 in frontotemporal lobar degeneration with partial volume correction. 11th Human Amyloid Imaging; 2017. p. 176.Google Scholar
- 29.Sander K, Lashley T, Gami P, Gendron T, Lythgoe MF, Rohrer JD, et al. 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. 2016;12:1116–24.CrossRefPubMedGoogle Scholar
- 32.Spina S, Schonhaut DR, Boeve BF, Seeley WW, Ossenkoppele R, O’Neil JP, et al. Frontotemporal dementia with the V337M MAPT mutation: tau-PET and pathology correlations. Neurology. 2017.Google Scholar
- 33.Hwang J, Kim JE, Park S-H, Roh JH, Lee J-H. A Non-fluent agrammatic primary progressive aphasia documented with an 18F–THK5351-PET. 2016 Annual Spring Meeting of Korean Dementia Association; 2016.Google Scholar
- 34.Lee H, Lee S-Y, Jeong HJ, Woo S-H, Lee K-M, Lee Y-B, et al. Tau PET imaging in patients with semantic variant primary progressive aphasia 35th 2016 Annual Autumn Meeting of the Korean Neurological Association; 2016.Google Scholar
- 35.Kim JE, Hwang J, Park S-H, Oh M, Kim JS, Lee J-H, et al. 18F–THK5351 PET findings indicatige of brain injury rather than presumtive pathology in FTLD. 35th 2016 Annual Autumn Meeting of the Korean Neurological Association; 2016. p. 171.Google Scholar
- 38.Kim JE, Hwang J, Park S-H, Ko MA, Lee Y, Lee J-H, et al. Combined [18F]Florbetaben Amyloid PET and [18F]THK-5351 Tau PET as a potential pathfinder in a patient with rapidly progressive dementia. 2016 Annual Spring Meeting of the Korean Dementia Association; 2016. p. 165.Google Scholar
- 41.Bevan-Jones WR, Cope TE, Jones PS, Passamonti L, Hong YT, Fryer TD, et al. [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. 2017.Google Scholar