Development of tau PET Imaging Ligands and their Utility in Preclinical and Clinical Studies
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The pathological features of Alzheimer’s disease are senile plaques which are aggregates of β-amyloid peptides and neurofibrillary tangles in the brain. Neurofibrillary tangles are aggregates of hyperphosphorylated tau proteins, and these induce various other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and chronic traumatic encephalopathy. In the case of Alzheimer’s disease, the measurement of neurofibrillary tangles associated with cognitive decline is suitable for differential diagnosis, disease progression assessment, and to monitor the effects of therapeutic treatment. This review discusses considerations for the development of tau ligands for imaging and summarizes the results of the first-in-human and preclinical studies of the tau tracers that have been developed thus far. The development of tau ligands for imaging studies will be helpful for differential diagnosis and for the development of therapeutic treatments for tauopathies including Alzheimer’s disease.
KeywordsTau Alzheimer’s disease Tauopathy Pet Imaging ligands Radiopharmaceutical
Compliance with Ethical Standards
Conflict of Interest
Authors Yoori Choi, Seunggyun Ha, Yun-Sang Lee, and Yun Kyung Kim declare that they have no conflict of interest. Author Dong Soo Lee has received research grants 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 (HI14C0466), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3344), and funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1277). Author Dong Jin Kim has received a research grant supported by the Brain Research Program through the National Research Foundation of Korea (NRF-2016M3C7A1913845).
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.
For this type of study formal consent is not required.
- 13.Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:280–92.CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment 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;7:270–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.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
- 36.Agdeppa EDKV, Liu J, Flores-Torres S, Satyamurthy N, Petric A, Cole GM, et al. Binding characteristics of Radiofluorinated 6-Dialkylamino-2-Naphthylethylidene derivatives as positron emission tomography imaging probes for β-amyloid plaques in Alzheimer’s disease. J Neurosci. 2001;21:RC189.PubMedGoogle Scholar
- 57.WashingtonUniversity. F 18 T807 Tau PET imaging of Alzheimer’s disease. ClinicalTrialsgov Identifier: NCT02414347. 2015.Google Scholar
- 61.Betthauser T, Lao PJ, Murali D, Barnhart TE, Furumoto S, Okamura N et al. In vivo comparison of tau radioligands 18F–THK-5351 and 18F–THK-5317. J Nucl Med. 2016.Google Scholar
- 62.Roche. Evaluation of [18F]RO6958948 as tracer for positron emission tomography (PET) imaging of Tau Burden in Alzheimer’s disease participants. ClinicalTrialsgov Identifier: NCT02792179. 2016.Google Scholar
- 64.Fawaz MV, Brooks AF, Rodnick ME, Carpenter GM, Shao X, Desmond TJ, et al. High affinity radiopharmaceuticals based upon lansoprazole for PET imaging of aggregated tau in Alzheimer’s disease and progressive supranuclear palsy: synthesis, preclinical evaluation, and lead selection. ACS Chem Neurosci. 2014;5:718–30.CrossRefPubMedPubMedCentralGoogle Scholar
- 65.Walji AM, Hostetler ED, Selnick H, Zeng Z, Miller P, Bennacef I, et al. Discovery of 6-(Fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18)F]-MK-6240): a positron emission tomography (PET) imaging agent for quantification of neurofibrillary tangles (NFTs). J Med Chem. 2016;59:4778–89.CrossRefPubMedGoogle Scholar
- 67.Genentech. Longitudinal evaluation of [18F]MNI-798 as a PET radioligand for imaging Tau in the brain of patients with Alzheimer’s disease compared to healthy volunteers. ClinicalTrialsgov Identifier: NCT02640092. 2015.Google Scholar