DOI QR코드

DOI QR Code

Review of the chemistry of first-generation Tau PET tracers

  • Farag, Ahmed Karam (RI Translational Research Team, Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Im, Changkeun (RI Translational Research Team, Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Kang, Choong Mo (RI Translational Research Team, Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Lee, Yong Jin (Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS))
  • Received : 2020.06.15
  • Accepted : 2020.06.26
  • Published : 2020.06.30

Abstract

Alzheimer's disease (AD) is one of the challenging conditions that have no cure, yet early diagnosis can help to control the disease. PET imaging of tau has several advantages, such as being a noninvasive, safe diagnostic technique that correlates directly with the disease progression. Many tau tracers have been reported to date; however, the chemical scaffolds of them fall in a narrow chemical window, and none was approved yet as none is entirely selective and sensitive to tau. These problems are being solved as new tracers emerge constantly. In this report, the first-generation tau tracers such as [11C]PBB3, 2-arylquinoline (THK) series, [18F]T808, and [18F]AV-1451 ([18F]T807) are reviewed from an organic and radiochemistry perspective; thus the most effective chemical approach to synthesize these tracers is discussed. This would help to design novel tracers which can meet the challenges faced by the current tracers.

Keywords

References

  1. Sengoku R. Aging and Alzheimer's disease pathology. Neuropathology 2020;40(1):22-29. https://doi.org/10.1111/neup.12626
  2. 2020 Alzheimer's disease facts and figures. Alzheimers Dement 2020;16:391-460.
  3. Singh H, Chawla V, Bala R, Dureja H. Current and future of Alzheimer's therapy with the best approach. CNS Neurol Disord Drug Targets 2020;19:1. https://doi.org/10.2174/187152731901200316111017
  4. Stower H. Searching for Alzheimer's disease therapies. Nat Med 2018;24(7):894-897. https://doi.org/10.1038/s41591-018-0127-2
  5. Guest FL, Rahmoune H, Guest PC. Early diagnosis and targeted treatment strategy for improved therapeutic outcomes in Alzheimer's disease. In: Guest P, editors. Reviews on new drug targets in age-related disorders. Advances in experimental medicine and biology, vol 1260 : Springer, Cham; 2020. p. 175-191.
  6. Blennow K. CSF biomarkers for Alzheimer's disease: Use in early diagnosis and evaluation of drug treatment. Expert Rev Mol Diagn 2005;5(5):661-672. https://doi.org/10.1586/14737159.5.5.661
  7. Ritchie C, Smailagic N, Noel-Storr AH, Ukoumunne O, Ladds EC, Martin S. CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 2017;3:CD010803.
  8. Uzuegbunam BC, Librizzi D, Hooshyar Yousefi B. PET Radiopharmaceuticals for Alzheimer's disease and Parkinson's disease diagnosis, the current and future landscape. Molecules 2020;25(4):977. https://doi.org/10.3390/molecules25040977
  9. Wilcock GK, Esiri MM. Plaques, tangles and dementia. A quantitative study. J Neurol Sci 1982;56(2-3):343-356. https://doi.org/10.1016/0022-510X(82)90155-1
  10. Mullane K, Williams M. Alzheimer's disease beyond amyloid: Can the repetitive failures of amyloid-targeted therapeutics inform future approaches to dementia drug discovery? Biochem Pharmacol 2020;177:113945. https://doi.org/10.1016/j.bcp.2020.113945
  11. Jack CR, Jr., Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010;9(1):119-128. https://doi.org/10.1016/S1474-4422(09)70299-6
  12. Congdon EE, Sigurdsson EM. Tau-targeting therapies for Alzheimer disease. Nature Reviews Neurology 2018;14(7):399-415. https://doi.org/10.1038/s41582-018-0013-z
  13. Leuzy A, Chiotis K, Lemoine L, Gillberg PG, Almkvist O, Rodriguez-Vieitez E, Nordberg A. Tau PET imaging in neurodegenerative tauopathies-still a challenge. Mol Psychiatry 2019;24(8):1112-1134. https://doi.org/10.1038/s41380-018-0342-8
  14. Ariza M, Kolb HC, Moechars D, Rombouts F, Andres JI. Tau positron emission tomography (PET) imaging: past, present, and future. J Med Chem 2015;58(11):4365-4382. https://doi.org/10.1021/jm5017544
  15. Wang YT, Edison P. Tau Imaging in Neurodegenerative Diseases Using Positron Emission Tomography. Curr Neurol Neurosci Rep 2019;19(7):45. https://doi.org/10.1007/s11910-019-0962-7
  16. Murugan NA, Chiotis K, Rodriguez-Vieitez E, Lemoine L, Agren H, Nordberg A. Cross-interaction of tau PET tracers with monoamine oxidase B: evidence from in silico modelling and in vivo imaging. Eur J Nucl Med Mol Imaging 2019;46(6):1369-1382. https://doi.org/10.1007/s00259-019-04305-8
  17. Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years. J Neuropathol Exp Neurol 2011;70(11):960-969. https://doi.org/10.1097/NEN.0b013e318232a379
  18. Chiotis K, Stenkrona P, Almkvist O, Stepanov V, Ferreira D, Arakawa R, Takano A, Westman E, Varrone A, Okamura N, Shimada H, Higuchi M, Halldin C, Nordberg A. Dual tracer tau PET imaging reveals different molecular targets for $^{11}C$-THK5351 and 11C-PBB3 in the Alzheimer brain. Eur J Nucl Med Mol Imaging 2018;45(9):1605-1617. https://doi.org/10.1007/s00259-018-4012-5
  19. Wood H. Alzheimer disease: [$^{11}C$]PBB3-a new PET ligand that identifies tau pathology in the brains of patients with AD. Nat Rev Neurol 2013;9(11):599. https://doi.org/10.1038/nrneurol.2013.216
  20. 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 MR. Radiosynthesis, photoisomerization, biodistribution, and metabolite analysis of $^{11}C$-PBB3 as a clinically useful PET probe for imaging of tau pathology. J Nucl Med 2014;55(9):1532-1538. https://doi.org/10.2967/jnumed.114.139550
  21. Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, Zhang MR, Trojanowski JQ, Lee VMY, Ono M, Masamoto K, Takano H, Sahara N, Iwata N, Okamura N, Furumoto S, Kudo Y, Chang Q, Saido TC, Takashima A, Lewis J, Jang MK, Aoki I, Ito H, Higuchi M. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 2013;79(6):1094-1108. https://doi.org/10.1016/j.neuron.2013.07.037
  22. Koga S, Ono M, Sahara N, Higuchi M, Dickson DW. Fluorescence and autoradiographic evaluation of tau PET ligand PBB3 to alpha-synuclein pathology. Mov Disord 2017;32(6):884-892. https://doi.org/10.1002/mds.27013
  23. Endo H, Shimada H, Sahara N, Ono M, Koga S, Kitamura S, Niwa F, Hirano S, Kimura Y, Ichise M, Shinotoh H, Zhang MR, Kuwabara S, Dickson DW, Toda T, Suhara T, Higuchi M. In vivo binding of a tau imaging probe, [$^{11}C$] PBB3, in patients with progressive supranuclear palsy. Mov Disord 2019;34(5):744-754. https://doi.org/10.1002/mds.27643
  24. Wang M, Gao M, Xu Z, Zheng QH. Synthesis of a PET tau tracer [$^{11}C$]PBB3 for imaging of Alzheimer's disease. Bioorg Med Chem Lett 2015;25(20):4587-4592. https://doi.org/10.1016/j.bmcl.2015.08.053
  25. Battistuzzi G, Cacchi S, Fabrizi G. An efficient palladiumcatalyzed synthesis of cinnamaldehydes from acrolein diethyl acetal and aryl iodides and bromides. Org Lett 2003;5(5):777-780. https://doi.org/10.1021/ol034071p
  26. Zhuang ZP, Kung MP, Kung HF. Synthesis of biphenyltrienes as probes for beta-amyloid plaques. J Med Chem 2006;49(9):2841-2844. https://doi.org/10.1021/jm051020k
  27. 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 Alzheimer's disease. J Neurosci 2005;25(47):10857-10862. https://doi.org/10.1523/JNEUROSCI.1738-05.2005
  28. Jonasson M, Wall A, Chiotis K, Saint-Aubert L, Wilking H, Sprycha M, Borg B, Thibblin A, Eriksson J, Sorensen J, Antoni G, Nordberg A, Lubberink M. Tracer kinetic analysis of (S)-18F-THK5117 as a PET tracer for assessing tau pathology. J Nucl Med 2016;57(4):574-581. https://doi.org/10.2967/jnumed.115.158519
  29. Chiotis K, Saint-Aubert L, Savitcheva I, Jelic V, Andersen P, Jonasson M, Eriksson J, Luberink M, Almkvist O, Wall A, Antoni G, Nordberg A. Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm. Eur J Nucl Med Mol Imaging 2016;43(9):1686-1699. https://doi.org/10.1007/s00259-016-3363-z
  30. Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N, Tago T, Hiraoka K, Watanuki S, Shidahara M, Miyake M, Ishikawa Y, Matsuda R, Inami A, Yoshikawa T, Funaki Y, Iwata R, Tashiro M, Yanai K, Arai H, Kudo Y. 18F-THK5351: A novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer Disease. J Nucl Med 2016;57(2):208-214. https://doi.org/10.2967/jnumed.115.164848
  31. Lemoine L, Gillberg PG, Svedberg M, Stepanov V, Jia Z, Huang J, Nag S, Tian H, Ghetti B, Okamura N, Higuchi M, Halldin C, Nordberg A. Comparative binding properties of the tau PET tracers THK5117, THK5351, PBB3, and T807 in postmortem Alzheimer brains. Alzheimers Res Ther 2017;9(1):96. https://doi.org/10.1186/s13195-017-0325-z
  32. Betthauser TJ, Lao PJ, Murali D, Barnhart TE, Furumoto S, Okamura N, Stone CK, Johnson SC, Christian BT. In vivo comparison of tau radioligands $^{18}F$-THK-5351 and 18F-THK-5317. J Nucl Med 2017;58(6):996-1002. https://doi.org/10.2967/jnumed.116.182980
  33. Okamura N, Furumoto S, Harada R, Tago T, Yoshikawa T, Fodero-Tavoletti M, Mulligan RS, Villemagne VL, 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(8):1420-1427. https://doi.org/10.2967/jnumed.112.117341
  34. Betthauser TJ, Ellison PA, Murali D, Lao PJ, Barnhart TE, Furumoto S, Okamura N, Johnson SC, Engle JW, Nickles RJ, Christian BT. Characterization of the radiosynthesis and purification of [$^{18}F$]THK-5351, a PET ligand for neurofibrillary tau. Appl Radiat Isot 2017;130:230-237. https://doi.org/10.1016/j.apradiso.2017.10.002
  35. Neelamegam R, Yokell DL, Rice PA, Furumoto S, Kudo Y, Okamura N, Fakhri GE. A report of the automated radiosynthesis of the tau positron emission tomography radiopharmaceutical, [$^{18}F$]-THK-5351. J Labelled Comp Radiopharm 2017;60(2):140-146. https://doi.org/10.1002/jlcr.3482
  36. Lee SJ, Oh SJ, Cho EH, Kim DH, Furumoto S, Okamura N, Kim JS. Full automatic synthesis of [$^{18}F$]THK-5351 for tau protein PET imaging in Alzheimer's disease patients: 1 year experience. J Radioanal Nucl Chem 2017;314(3):1587-1593. https://doi.org/10.1007/s10967-017-5573-7
  37. Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Szardenings AK, Wang E, Walsh JC, Xia C, Yu C, Zhao T, Kolb HC. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis 2012;31(3):601-612. https://doi.org/10.3233/JAD-2012-120712
  38. Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Su H, Szardenings AK, Walsh JC, Wang E, Yu C, Zhang W, Zhao T, Kolb HC. [$^{18}F$]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement 2013;9(6):666-676. https://doi.org/10.1016/j.jalz.2012.11.008
  39. Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu F, Xia C, Shankle WR, Lerner AJ, Su MY, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimers Dis 2014;38(1):171-184.
  40. Gao M, Wang M, Zheng QH. Fully automated synthesis of [$^{18}F$]T807, a PET tau tracer for Alzheimer's disease. Bioorg Med Chem Lett 2015;25(15):2953-2957. https://doi.org/10.1016/j.bmcl.2015.05.035
  41. Shoup TM, Yokell DL, Rice PA, Jackson RN, Livni E, Johnson KA, Brady TJ, Vasdev N. A concise radiosynthesis of the tau radiopharmaceutical, [$^{18}F$]T807. J Labelled Comp Radiopharm 2013;56(14):736-740. https://doi.org/10.1002/jlcr.3098
  42. Mossine AV, Brooks AF, Henderson BD, Hockley BG, Frey KA, Scott PJH. An updated radiosynthesis of [$^{18}F$] AV1451 for tau PET imaging. EJNMMI Radiopharm Chem 2017;2(1):7. https://doi.org/10.1186/s41181-017-0027-7
  43. Holt DP, Ravert HT, Dannals RF. Synthesis and quality control of [$^{18}F$F]T807 for tau PET imaging. J Labelled Comp Radiopharm 2016;59(10):411-415. https://doi.org/10.1002/jlcr.3425
  44. Gao M, Wang M, Zheng QH. Concise and high-yield synthesis of T808 and T808P for radiosynthesis of [$^{18}F$]-T808, a PET tau tracer for Alzheimer's disease. Bioorg Med Chem Lett 2014;24(1):254-257. https://doi.org/10.1016/j.bmcl.2013.11.025
  45. Szardenings AK, Zhang W, Kolb HC, Cashion DK, Chen G, Kasi D, Liu C, Sinha A, Wang E, Yu C, Gangadharmath UB, Walsh JC. Patent US20110182812A1. 2011.
  46. Cashion DK, Chen G, Kasi D, Kolb HC, Liu C, Sinha A, Szardenings AK, Wang E, Yu C, Zhang W, Gangadharmath UB, Walsh JC. Patent WO2011119565A1. 2011.
  47. Fitzpatrick AWP, Falcon B, He S, Murzin AG, Murshudov G, Garringer HJ, Crowther RA, Ghetti B, Goedert M, Scheres SHW. Cryo-EM structures of tau filaments from Alzheimer's disease. Nature 2017;547(7662):185-190. https://doi.org/10.1038/nature23002