Journal of the Korean Society of Radiology (대한영상의학회지)

The Korean Society of Radiology (대한영상의학회)
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Recent Updates on PET Imaging in Neurodegenerative Diseases

퇴행성 뇌질환에서 PET의 발전과 임상적 적용 및 최신 동향

  • Yu Kyeong Kim (Department of Nuclear Medicine, Seoul National University Boramae Medical Center)
  • 김유경 (서울특별시 보라매병원 핵의학과)
  • Received : 2022.04.16
  • Accepted : 2022.05.16
  • Published : 2022.05.01
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Abstract

Over the past decades, the immense clinical need for early detection methods and treatments for dementia has become a priority worldwide. The advances in PET biomarkers play increasingly important roles in understanding disease mechanisms by demonstrating the protein pathology underlying dementia in the brain. Amyloid-β and tau deposition in PET images are now key diagnostic biomarkers for the Alzheimer's disease continuum. The inclusion of biomarkers in the diagnostic criteria has achieved a paradigm shift in facilitating early differential diagnosis, predicting disease prognosis, and influencing clinical management. Furthermore, in vivo images showing pathology could become prognostic as well as surrogate biomarkers in therapeutic trials. In this review, we focus on recent developments in radiotracers for amyloid-β and tau PET imaging in Alzheimer's disease and other neurodegenerative diseases. Further, we introduce their potential application as future perspectives.

양전자방출단층촬영(PET)을 이용한 단백질병리의 생체영상기술은 퇴행성 치매의 질병 기전을 이해하는데 필요한 정보를 제공할 뿐 아니라, 질병의 조기 발견과 치료법 개발에서 중요한 역할을 수행하고 있다. 베타아밀로이드와 타우 PET 영상은 인체 뇌병리에 기반한 알츠하이머병 연속체에 대한 진단 바이오마커로 확립되어 조기진단과 감별진단을 용이하게 하고, 질병 예후를 예측하고 있다. 또한, 치매치료제 개발에서 예후 및 대리 바이오마커로의 역할이 커지고 있다. 이 종설에서는 치매를 유발하는 알츠하이머병 및 기타 퇴행성 뇌질환에서 베타아밀로이드와 타우 단백질의 뇌축적을 영상화하는 PET의 최근 임상적 적용과 최근 동향을 살펴보고, 잠재적 유용성을 소개하고자 한다.

Keywords

Acknowledgement

This study was supported by a research grant from the National Research Foundation (NRF) funded by the Ministry of Education, Science and Technology (MEST) in Korea (2018R1A5A2025964).

References

  1. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016;87:539-547 
  2. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement 2018;14:535-562 
  3. Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 2002;10:24-35 
  4. Klunk WE, Wang Y, Huang GF, Debnath ML, Holt DP, Shao L, et al. The binding of 2-(4'-methylaminophenyl) benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci 2003;23:2086-2092 
  5. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 2004;55:306-319 
  6. Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 2011;305:275-283 
  7. Curtis C, Gamez JE, Singh U, Sadowsky CH, Villena T, Sabbagh MN, et al. Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density. JAMA Neurol 2015;72:287-294 
  8. Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, et al. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: phase 3 study. Alzheimers Dement 2015;11:964-974 
  9. Byun BH, Kim BI, Park SY, Ko IO, Lee KC, Kim KM, et al. Head-to-head comparison of 11C-PiB and 18F-FC119S for Aβ imaging in healthy subjects, mild cognitive impairment patients, and Alzheimer's disease patients. Medicine (Baltimore) 2017;96:e6441 
  10. Sundaram GS, Dhavale DD, Prior JL, Yan P, Cirrito J, Rath NP, et al. Fluselenamyl: a novel benzoselenazole derivative for PET detection of amyloid plaques (Aβ) in Alzheimer's disease. Sci Rep 2016;6:35636 
  11. Morris E, Chalkidou A, Hammers A, Peacock J, Summers J, Keevil S. Diagnostic accuracy of (18)F amyloid PET tracers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2016;43:374-385 
  12. U.S. Food & Drug Administration. Drug@FDA: FDA-Arrved Drugs. Amyvid/labells for NDA202008. Available at. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202008s000lbl.pdf. Published 2012. Accessed Mar 4, 2022 
  13. U.S. Food & Drug Administration. Drug@FDA: FDA-arrved drugs. Neuraceq/labels for NDA204677. Available at. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204677s000lbl.pdf. Published 2014. Accessed Mar 4, 2022 
  14. U.S. Food & Drug Administration. Drug@FDA: FDA-arrved drugs. Vizamyl/labels for NDA203137. Available at. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203137s000lbl.pdf. Published 2013. Accessed Mar 4, 2022 
  15. Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BN, et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA 2015;313:1939-1949 
  16. Cohen AD, McDade E, Christian B, Price J, Mathis C, Klunk W, et al. Early striatal amyloid deposition distinguishes Down syndrome and autosomal dominant Alzheimer's disease from late-onset amyloid deposition. Alzheimers Dement 2018;14:743-750 
  17. Hanseeuw BJ, Betensky RA, Mormino EC, Schultz AP, Sepulcre J, Becker JA, et al. PET staging of amyloidosis using striatum. Alzheimers Dement 2018;14:1281-1292 
  18. Klunk WE, Koeppe RA, Price JC, Benzinger TL, Devous MD Sr, Jagust WJ, et al. The Centiloid project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement 2015;11:1-15.e1-e4 
  19. Burnham SC, Bourgeat P, Dore V, Savage G, Brown B, Laws S, et al. Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study. Lancet Neurol 2016;15:1044-1053 
  20. Bourgeat P, Dore V, Fripp J, Ames D, Masters CL, Salvado O, et al. Implementing the centiloid transformation for 11C-PiB and β-amyloid 18F-PET tracers using CapAIBL. Neuroimage 2018;183:387-393 
  21. La Joie R, Ayakta N, Seeley WW, Borys E, Boxer AL, DeCarli C, et al. Multisite study of the relationships between antemortem [11C] PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. Alzheimers Dement 2019;15:205-216 
  22. Amadoru S, Dore V, McLean CA, Hinton F, Shepherd CE, Halliday GM, et al. Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer's disease. Alzheimers Res Ther 2020;12:22 
  23. van der Kall LM, Truong T, Burnham SC, Dore V, Mulligan RS, Bozinovski S, et al. Association of β-amyloid level, clinical progression, and longitudinal cognitive change in normal older individuals. Neurology 2021;96:e662-e670 
  24. Salvado G, Molinuevo JL, Brugulat-Serrat A, Falcon C, Grau-Rivera O, Suarez-Calvet M, et al. Centiloid cut-off values for optimal agreement between PET and CSF core AD biomarkers. Alzheimers Res Ther 2019;11:27 
  25. Schmidt ME, Chiao P, Klein G, Matthews D, Thurfjell L, Cole PE, et al. The influence of biological and technical factors on quantitative analysis of amyloid PET: points to consider and recommendations for controlling variability in longitudinal data. Alzheimers Dement 2015;11:1050-1068 
  26. Kim JP, Chun MY, Kim SJ, Jang H, Kim HJ, Jeong JH, et al. Distinctive temporal trajectories of Alzheimer's disease biomarkers according to sex and APOE genotype: importance of striatal amyloid. Front Aging Neurosci 2022;14:829202 
  27. Beach TG, Sue LI, Walker DG, Sabbagh MN, Serrano G, Dugger BN, et al. Striatal amyloid plaque density predicts Braak neurofibrillary stage and clinicopathological Alzheimer's disease: implications for amyloid imaging. J Alzheimers Dis 2012;28:869-876 
  28. Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol 2012;11:669-678 
  29. Landau SM, Horng A, Fero A, Jagust WJ; Alzheimer's Disease Neuroimaging Initiative. Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI. Neurology 2016;86:1377-1385 
  30. Chetelat G, Ossenkoppele R, Villemagne VL, Perrotin A, Landeau B, Mezenge F, et al. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease. Brain 2016;139(Pt 9):2528-2539 
  31. Jack CR Jr, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, et al. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol 2012;71:765-775 
  32. Li Z, Li K, Luo X, Zeng Q, Zhao S, Zhang B, et al. Distinct brain functional impairment patterns between suspected non-Alzheimer disease pathophysiology and Alzheimer's disease: a study combining static and dynamic functional magnetic resonance imaging. Front Aging Neurosci 2020;12:550664 
  33. Paulson OB, Hasselbalch SG, Rostrup E, Knudsen GM, Pelligrino D. Cerebral blood flow response to functional activation. J Cereb Blood Flow Metab 2010;30:2-14 
  34. Vanhoutte M, Landeau B, Sherif S, de la Sayette V, Dautricourt S, Abbas A, et al. Evaluation of the early-phase [18F] AV45 PET as an optimal surrogate of [18F] FDG PET in ageing and Alzheimer's clinical syndrome. Neuroimage Clin 2021;31:102750 
  35. Hsiao IT, Huang CC, Hsieh CJ, Hsu WC, Wey SP, Yen TC, et al. Correlation of early-phase 18F-florbetapir (AV45/Amyvid) PET images to FDG images: preliminary studies. Eur J Nucl Med Mol Imaging 2012;39:613-620 
  36. Daerr S, Brendel M, Zach C, Mille E, Schilling D, Zacherl MJ, et al. Evaluation of early-phase [18F]-florbetaben PET acquisition in clinical routine cases. Neuroimage Clin 2017;14:77-86 
  37. Jeong J, Jeong YJ, Park KW, Kang DY. Correlation of early-phase F-18 florapronal PET with F-18 FDG PET in Alzheimer's disease and normal brain. Nucl Med Mol Imaging 2019;53:328-333 
  38. Ottoy J, Verhaeghe J, Niemantsverdriet E, De Roeck E, Wyffels L, Ceyssens S, et al. 18F-FDG PET, the early phases and the delivery rate of 18F-AV45 PET as proxies of cerebral blood flow in Alzheimer's disease: validation against 15O-H2O PET. Alzheimers Dement 2019;15:1172-1182 
  39. Yoon HJ, Kim BS, Jeong JH, Kim GH, Park HK, Chun MY, et al. Dual-phase 18F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease. Neuroimage Clin 2021;31:102773 
  40. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Alzheimer's disease: developing drugs for the treatment of early stage disease. Available at. https://isctm.org/public_access/FDAGuidance_AD_Developing_Drugs_Early_Stage_Treatment.pdf. Published 2013. Accessed Mar 4, 2022 
  41. Rinne JO, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 2010;9:363-372 
  42. Ostrowitzki S, Lasser RA, Dorflinger E, Scheltens P, Barkhof F, Nikolcheva T, et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. Alzheimers Res Ther 2017;9:95 
  43. Lowe SL, Duggan Evans C, Shcherbinin S, Cheng YJ, Willis BA, Gueorguieva I, et al. Donanemab (LY3002813) phase 1b study in Alzheimer's disease: rapid and sustained reduction of brain amyloid measured by florbetapir F18 imaging. J Prev Alzheimers Dis 2021;8:414-424 
  44. Mintun MA, Lo AC, Duggan Evans C, Wessels AM, Ardayfio PA, Andersen SW, et al. Donanemab in early Alzheimer's disease. N Engl J Med 2021;384:1691-1704 
  45. Cho H, Choi JY, Hwang MS, Lee SH, Ryu YH, Lee MS, et al. Subcortical 18F-AV-1451 binding patterns in progressive supranuclear palsy. Mov Disord 2017;32:134-140 
  46. Leuzy A, Smith R, Ossenkoppele R, Santillo A, Borroni E, Klein G, et al. Diagnostic performance of RO948 F 18 tau positron emission tomography in the differentiation of Alzheimer disease from other neurodegenerative disorders. JAMA Neurol 2020;77:955-965 
  47. Scholl M, Maass A, Mattsson N, Ashton NJ, Blennow K, Zetterberg H, et al. Biomarkers for tau pathology. Mol Cell Neurosci 2019;97:18-33 
  48. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239-259 
  49. Ossenkoppele R, Schonhaut DR, Scholl M, Lockhart SN, Ayakta N, Baker SL, et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. Brain 2016;139(Pt 5):1551-1567 
  50. Schwarz AJ, Yu P, Miller BB, Shcherbinin S, Dickson J, Navitsky M, et al. Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages. Brain 2016;139(Pt 5):1539-1550 
  51. Chen SD, Lu JY, Li HQ, Yang YX, Jiang JH, Cui M, et al. Staging tau pathology with tau PET in Alzheimer's disease: a longitudinal study. Transl Psychiatry 2021;11:483 
  52. Pascoal TA, Therriault J, Benedet AL, Savard M, Lussier FZ, Chamoun M, et al. 18F-MK-6240 PET for early and late detection of neurofibrillary tangles. Brain 2020;143:2818-2830 
  53. Ossenkoppele R, Rabinovici GD, Smith R, Cho H, Scholl M, Strandberg O, et al. Discriminative accuracy of [18F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders. JAMA 2018;320:1151-1162 
  54. Leuzy A, Smith R, Cullen NC, Strandberg O, Vogel JW, Binette AP, et al. Biomarker-based prediction of longitudinal tau positron emission tomography in Alzheimer disease. JAMA Neurol 2022;79:149-158 
  55. Leuzy A, Pascoal TA, Strandberg O, Insel P, Smith R, Mattsson-Carlgren N, et al. A multicenter comparison of [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis. Eur J Nucl Med Mol Imaging 2021;48:2295-2305 
  56. Krishnadas N, Dore V, Groot C, Lamb F, Bourgeat P, Burnham SC, et al. Mesial temporal tau in amyloid-β -negative cognitively normal older persons. Alzheimers Res Ther 2022;14:51 
  57. Rubinski A, Tosun D, Franzmeier N, Neitzel J, Frontzkowski L, Weiner M, et al. Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex across the Alzheimer's continuum. Neurobiol Aging 2021;102:111-118 
  58. Lu M, Pontecorvo MJ, Devous MD Sr, Arora AK, Galante N, McGeehan A, et al. Aggregated tau measured by visual interpretation of flortaucipir positron emission tomography and the associated risk of clinical progression of mild cognitive impairment and Alzheimer disease: results from 2 phase III clinical trials. JAMA Neurol 2021;78:445-453 
  59. Jack CR, Wiste HJ, Weigand SD, Therneau TM, Lowe VJ, Knopman DS, et al. Predicting future rates of tau accumulation on PET. Brain 2020;143:3136-3150 
  60. Vogel JW, Young AL, Oxtoby NP, Smith R, Ossenkoppele R, Strandberg OT, et al. Four distinct trajectories of tau deposition identified in Alzheimer's disease. Nat Med 2021;27:871-881