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SPECT and PET imaging in Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Beta-amyloid (Aβ) deposition and neurofibrillary tangles (NFTs) of abnormal hyperphosphorylated tau protein are the pathological hallmarks of the disease, accompanied by other pathological processes such as microglia activation. Functional and molecular nuclear medicine imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques provides valuable information about the underlying pathological processes, many years before the appearance of clinical symptoms. Nuclear neuroimaging in AD has made great progress in the past two decades and has extended beyond the traditional role of brain perfusion and glucose metabolism evaluation. Intense efforts in radiopharmaceuticals research have led to the development of various probes able to detect Aβ deposits, tau protein accumulation, microglia activation and neuroinflammation. As a result, SPECT and PET have proposed to serve as biomarkers in recently revised diagnostic clinical criteria for the early diagnosis of AD and the prediction of progression to AD in mild cognitive impairment (MCI) subjects.

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Fig. 1
Fig. 2

(This research was originally published in JNM. Author(s): Rowe CC, Jones G, Doré V, Pejoska S, Margison L, Mulligan RS, Chan JG, Young K, Villemagne VL. Title: “Standardized Expression of 18F-NAV4694 and 11C-PiB β-Amyloid PET Results with the Centiloid Scale.” J Nucl Med. 2016;57(8):1233-7© by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

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References

  1. Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006;368:387–403.

    Article  CAS  PubMed  Google Scholar 

  2. Alzheimer’s Association. 2010 Alzheimer’s disease facts and figures. Alzheimers Dement. 2010;6:158–94.

    Article  Google Scholar 

  3. Farias ST, Mungas D, Reed BR, Harvey D, De Carli C. Progression of mild cognitive impairment to dementia in clinic- vs community-based cohorts. Arch Neurol. 2009;66:1151–7.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9:119–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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 work groups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jack CR Jr. Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play. Radiology. 2012;263:344–61.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Valotassiou V, Wozniak G, Sifakis N, Demakopoulos N, Georgoulias P. Radiopharmaceuticals in neurological and psychiatric disorders. Curr Clin Pharmacol. 2008;3:99–107.

    Article  CAS  PubMed  Google Scholar 

  8. Valotassiou V, Archimandritis S, Sifakis N, Papatriantafyllou J, Georgoulias P. Alzheimer’s disease: SPECT and PET tracers for beta-amyloid imaging. Curr Alzheimer Res. 2010;7:477–86.

    Article  CAS  PubMed  Google Scholar 

  9. Mier W, Mier D. Advantages in functional imaging of the brain. Front Hum Neurosci. 2015;9:249.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Villringer A, Dirnagl U. Coupling of brain activity and cerebral blood flow: basis of functional neuroimaging. Cerebrovasc Brain Metab Rev. 1995;7:240–76.

    CAS  PubMed  Google Scholar 

  11. Valotassiou V, Papatriantafyllou J, Sifakis N, Tzavara C, Tsougos I, Psimadas D, et al. Clinical evaluation of brain perfusion SPECT with Brodmann areas mapping in early diagnosis of Alzheimer’s disease. J Alzheimer’s Dis. 2015;47:773–85.

    Article  Google Scholar 

  12. Valotassiou V, Papatriantafyllou J, Sifakis N, Tzavara C, Tsougos I, Kapsalaki E, et al. Perfusion SPECT studies with mapping of Brodmann areas in differentiating Alzheimer’s disease from frontotemporal degeneration syndromes. Nucl Med Commun. 2012;33:1267–76.

    Article  PubMed  Google Scholar 

  13. Foster NL, Heidebrink JL, Clark CM, Jagust WJ, Arnold SE, Barbas NR, et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer’s disease. Brain. 2007;130:2616–35.

    Article  PubMed  Google Scholar 

  14. Vitali P, Migliaccio R, Agosta F, Rosen HJ, Geschwind MD. Neuroimaging in dementia. Semin Neurol. 2008;28:467–83.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mosconi L, Tsui WH, Herholz K, Pupi A, Drzezga A, Lucignani G, et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer’s disease, and other dementias. J Nucl Med. 2008;49:390–8.

    Article  PubMed  Google Scholar 

  16. Bloudek LM, Spackman DE, Blankenburg M, Sullivan SD. Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimer’s disease. J Alzheimers Dis. 2011;26:627–45.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang D, Shen D, Alzheimer’s Disease Neuroimaging Initiative. Predicting future clinical changes of MCI patients using longitudinal and multimodal biomarkers. PLoS One. 2012;7:33182.

    Article  CAS  Google Scholar 

  18. Frisoni GB, Bocchetta M, Chételat G, Rabinovici GD, de Leon MJ, Kaye J, ISTAART’s NeuroImaging Professional Interest Area, et al. Imaging markers for Alzheimer disease: which vs how. Neurology. 2013;81:487–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pagani M, Nobili F, Morbelli S, Arnaldi D, Giuliani A, Öberg J, et al. Early identification of MCI converting to AD: a FDG PET study. Eur J Nucl Med Mol Imaging. 2017;44:2042–52.

    Article  CAS  PubMed  Google Scholar 

  20. Talbot PR, Lloyd JJ, Snowden JS, Neary D, Testa HJ. Choice of reference region in the quantification of single-photon emission tomography in primary degenerative dementia. Eur J Nucl Med. 1994;21:503–8.

    Article  CAS  PubMed  Google Scholar 

  21. Acton PD. Image analysis in brain SPECT and PET. In: Ell PJ, Gambhir S, editors. Nuclear medicine in clinical diagnosis and treatment. 3rd edition. London: Churchill Livingstone; 2004. p. 1341–53.

    Google Scholar 

  22. Matsuda H, Mizumura S, Nagao T, Ota T, Iizuka T, Nemoto K, et al. Automated discrimination between very early Alzheimer disease and controls using an easy Z-score imaging system for multicenter brain perfusion single-photon emission tomography. AJNR Am J Neuroradiol. 2007;28:731–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging. 1997;18:351–7.

    Article  CAS  PubMed  Google Scholar 

  24. Agdeppa ED, Kepe V, Liu J, Small GW, Huang SC, Petric A, et al. 2-Dialkylamino-6-acylmalononitrile substituted naphthalenes (DDNP analogs): novel diagnostic and therapeutic tools in Alzheimer’s disease. Mol Imaging Biol. 2003;5:404–17.

    Article  PubMed  Google Scholar 

  25. 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;55:306–19.

    Article  CAS  PubMed  Google Scholar 

  26. Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta amyloid burden in aging and dementia. Neurology. 2007;68:1718–25.

    Article  CAS  PubMed  Google Scholar 

  27. Niedowicz DM, Beckett TL, Matveev S, Weidner AM, Baig I, Kryscio RJ, et al. Pittsburgh compound b and the postmortem diagnosis of Alzheimer’s disease. Ann Neurol. 2012;72:564–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cho H, Seo SW, Kim JH, Suh MK, Lee JH, Choe YS, et al. Amyloid deposition in early onset versus late onset Alzheimer’s disease. J Alzheimers Dis. 2013;35:813–21.

    Article  PubMed  CAS  Google Scholar 

  29. Rabinovici GD, Furst AJ, O’Neil JP, Racine CA, Mormino EC, Baker SL, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology. 2007;68:1205–12.

    Article  CAS  PubMed  Google Scholar 

  30. Forsberg A, Engler H, Almkvist O, Blomquist G, Hagman G, Wall A, et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging. 2008;29:1456–65.

    Article  CAS  PubMed  Google Scholar 

  31. Lim YY, Maruff P, Pietrzak RH, Ames D, Ellis KA, Harrington K, et al. Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer’s disease. Brain. 2014;137:221–31.

    Article  PubMed  Google Scholar 

  32. Okello A, Koivunen J, Edison P, Archer HA, Turkheimer FE, Någren K, et al. Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology. 2009;73:754–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Villemagne VL, Pike KE, Chételat G, Ellis KA, Mulligan RS, Bourgeat P, et al. Longitudinal assessment of Ab and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69:181–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Grimmer T, Wutz C, Drzezga A, Förster S, Förstl H, Ortner M, et al. The usefulness of amyloid imaging in predicting the clinical outcome after two years in subjects with mild cognitive impairment. Curr Alzheimer Res. 2013;10:82–5.

    CAS  PubMed  Google Scholar 

  35. Ma Y, Zhang S, Li J, Zheng DM, Guo Y, Feng J, et al. Predictive accuracy of amyloid imaging for progression from mild cognitive impairment to Alzheimer disease with different lengths of follow-up: a meta-analysis [Corrected]. Medicine (Baltimore). 2014;93:150.

    Article  CAS  Google Scholar 

  36. Landau SM, Breault C, Joshi AD, Pontecorvo M, Mathis CA, Jagust WJ, et al. Amyloid-β imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. J Nucl Med. 2013;54:70–7.

    Article  CAS  PubMed  Google Scholar 

  37. Wolk DA, Zhang Z, Boudhar S, Clark CM, Pontecorvo MJ, Arnold SE. Amyloid imaging in Alzheimer’s disease: comparison of florbetapir and Pittsburgh compound-B positron emission tomography. J Neurol Neurosurg Psychiatry. 2012;83:923–6.

    Article  PubMed  Google Scholar 

  38. 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-beta plaques: a prospective cohort study. Lancet Neurol. 2012;11:669–78.

    Article  CAS  PubMed  Google Scholar 

  39. Doraiswamy PM, Sperling RA, Johnson K, Reiman EM, Wong TZ, Sabbagh MN, et al. Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study. Mol Psychiatry. 2014;19:1044–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dugger BN, Clark CM, Serrano G, Mariner M, Bedell BJ, Coleman RE, et al. Neuropathologic heterogeneity does not impair florbetapir positron emission tomography postmortem correlates. J Neuropathol Exp Neurol. 2014;73:72–80.

    Article  PubMed  Google Scholar 

  41. Barthel H, Luthardt J, Becker G, Patt M, Hammerstein E, Hartwig K, et al. Individualized quantification of brain β-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.

    Article  CAS  PubMed  Google Scholar 

  42. Barthel H, Gertz HJ, Dresel S, Peters O, Bartenstein P, Buerger K, et al. Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011;10:424–35.

    Article  CAS  PubMed  Google Scholar 

  43. Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, et al. Florbetaben PET imaging to detect amyloid plaques in Alzheimer disease: phase 3 study. Alzheimers Dement. 2015;11:964–74.

    Article  PubMed  Google Scholar 

  44. Villemagne VL, Ong K, Mulligan RS, Holl G, Pejoska S, Jones G, et al. Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias. J Nucl Med. 2011;52:1210–7.

    Article  PubMed  Google Scholar 

  45. Ong K, Villemagne VL, Bahar-Fuchs A, Lamb F, Chételat G, Raniga P, et al. (18)F-florbetaben Aβ imaging in mild cognitive impairment. Alzheimers Res Ther. 2013;5:4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hatashita S, Yamasaki H, Suzuki Y, Tanaka K, Wakebe D, Hayakawa H. [18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2014;41:290–300.

    Article  CAS  PubMed  Google Scholar 

  47. Duff K, Foster NL, Dennett K, Hammers DB, Zollinger LV, Christian PE, et al. Amyloid deposition and cognition in older adults: the effects of premorbid intellect. Arch Clin Neuropsychol. 2013;28:665–71.

    Article  PubMed  PubMed Central  Google Scholar 

  48. 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;43:374–85.

    Article  CAS  PubMed  Google Scholar 

  49. Marchant NL, Reed BR, DeCarli CS, Madison CM, Weiner MW, Chui HC, et al. Cerebrovascular disease, β-amyloid, and cognition in aging. Neurobiol Aging. 2012;33:1006-e25–36.

    Article  CAS  Google Scholar 

  50. Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31:1275–83.

    Article  PubMed  Google Scholar 

  51. Hatashita S, Yamasaki H. Clinically different stages of Alzheimer’s disease associated by amyloid deposition with 11C-PIB PET imaging. J Alzheimers Dis. 2010;21:995–1003.

    Article  PubMed  Google Scholar 

  52. Richards D, Sabbagh MN. Florbetaben for PET imaging of beta amyloid plaques in the brain. Neurol Ther. 2014;3:79–88.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Svedberg MM, Hall H, Hellström-Lindahl E, Estrada S, Guan Z, Nordberg A, et al. [11C]PIB-amyloid binding and levels of Aβ40 and Aβ42 in postmortem brain tissue from Alzheimer patients. Neurochem Int. 2009;54:347–57.

    Article  CAS  PubMed  Google Scholar 

  54. Klunk WE, Koeppe RA, Price JC, Benzinger TL, Devous Sr MD, Jagust WJ, et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11:1–15.

    Article  PubMed  Google Scholar 

  55. Rowe CC, Jones G, Doré V, Pejoska S, Margison L, Mulligan RS, et al. Standardized expression of 18F-NAV4694 and 11C-PiB β-amyloid PET results with the Centiloid Scale. J Nucl Med. 2016;57:1233–7.

    Article  CAS  PubMed  Google Scholar 

  56. Rowe CC, Doré V, Jones G. 18F-Florbetaben PET beta-amyloid binding expressed in centiloids. Eur J Nucl Med Mol Imaging. 2017;44:2053–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Anand K, Sabbagh M. Amyloid imaging: poised for integration into medical practice. Neurotherapeutics. 2017;14:54–61.

    Article  CAS  PubMed  Google Scholar 

  58. Yousefi BH, von Reutern B, Scherübl D, Manook A, Schwaiger M, Grimmer T, et al. FIBT versus florbetaben and PiB: a preclinical comparison study with amyloid-PET in transgenic mice. EJNMMI Res. 2015;5:20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Chen CJ, Bando K, Ashino H, Taguchi K, Shiraishi H, Shima K, et al. In vivo SPECT imaging of amyloid-β deposition with radioiodinated imidazo[1,2-a]pyridine derivative DRM106 in a mouse model of Alzheimer’s disease. J Nucl Med. 2015;56:120–6.

    Article  CAS  PubMed  Google Scholar 

  60. Maya Y, Okumura Y, Kobayashi R, Onishi T, Shoyama Y, Barret O, et al. Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-β. Brain. 2016;139:193–203.

    Article  PubMed  Google Scholar 

  61. Villemagne VL, Okamura N. In vivo tau imaging: obstacles and progress. Alzheimers Dement. 2014;10:254–64.

    Google Scholar 

  62. Schafer KN, Kim S, Matzavinos A, Kuret J. Selectivity requirements for diagnostic imaging of neurofibrillary lesions in Alzheimer’s disease: a simulation study. Neuroimage. 2012;60:1724–33.

    Article  PubMed  Google Scholar 

  63. Bischof GN, Endepols H, van Eimeren T, Drzezga A. Tau-imaging in neurodegeneration. Methods. 2017;130:114–23.

    Article  CAS  PubMed  Google Scholar 

  64. Villemagne VL, Fodero-Tavoletti MT, Masters CL, Rowe CC. Tau imaging: early progress and future directions. Lancet Neurol. 2015;14:114–24.

    Article  PubMed  Google Scholar 

  65. Ittner LM, Gotz J. Amyloid-beta and tauea toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci. 2011;12:65–72.

    Article  CAS  PubMed  Google Scholar 

  66. Zimmer ER, Leuzy A, Gauthier S, Rosa-Neto P. Developments in tau PET imaging. Can J Neurol Sci. 2014;41:547–53.

    Article  PubMed  Google Scholar 

  67. Fodero-Tavoletti MT, Okamura N, Furumoto S, Mulligan RS, Connor AR, McLean CA, et al. 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer’s disease. Brain. 2011;134:1089–100.

    Article  PubMed  Google Scholar 

  68. Villemagne VL, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Hodges J, Harada R, et al. In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2014;41:816–26.

    Article  CAS  PubMed  Google Scholar 

  69. Okamura N, Furumoto S, Harada R, Tago T, Yoshikawa T, Fodero-Tavoletti M, et al. Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. J Nucl Med. 2013;54:1420–7.

    Article  CAS  PubMed  Google Scholar 

  70. Okamura N, Furumoto S, Fodero-Tavoletti MT, Mulligan RS, Harada R, Yates P, et al. Non-invasive assessment of Alzheimer’s disease neurofibrillary pathology using 18F-THK5105 PET. Brain. 2014;137:1762–71.

    Article  PubMed  Google Scholar 

  71. Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N, et al. [(18)F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2015;42:1052–61.

    Article  CAS  PubMed  Google Scholar 

  72. Lemoine L, Saint-Aubert L, Marutle A, Antoni G, Eriksson JP, Ghetti B, et al. Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue. Acta Neuropathol Commun. 2015;3:40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Chiotis K, Saint-Aubert L, Savitcheva I, Jelic V, Andersen P, Jonasson M, et al. Imaging in-vivo tau pathology in Alzheimer’s disease with THK5317 PET in a multimodal paradigm. Eur J Nucl Med Mol Imaging. 2016;43:1686–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lockhart SN, Baker SL, Okamura N, Furukawa K, Ishiki A, Furumoto S, et al. Dynamic PET measures of tau accumulation in cognitively normal older adults and Alzheimer’s disease patients measured using [18F] THK-5351. PLoS One. 2016;11:e0158460.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Tago T, Furumoto S, Okamura N, Harada R, Ishikawa Y, Arai H, et al. Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging. J Label Compd Radiopharm. 2014;57:18–24.

    Article  CAS  Google Scholar 

  76. Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34:457–68.

    Article  CAS  PubMed  Google Scholar 

  77. Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu F, Xia C, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimers Dis. 2014;38:171–84.

    Article  PubMed  Google Scholar 

  78. Mintun M, Schwarz A, Joshi A, Shcherbinin S, Chien D, Elizarov A, et al. Exploratory analyses of regional human brain distribution of the PET tau tracer F18- labeled T807 (AV-1541) in subjects with normal cognitive function or cognitive impairment thought to be due to Alzheimer’s disease. Alzheimers Dement. 2013;9:842.

    Article  Google Scholar 

  79. Pontecorvo MJ, Devous Sr MD, Navitsky M, Lu M, Salloway S, Schaerf FW, et al. Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain. 2017;140:748–63.

    PubMed  PubMed Central  Google Scholar 

  80. Hashimoto H, Kawamura K, Igarashi N, Takei M, Fujishiro T, Aihara Y, et al. Radiosynthesis, photoisomerization, biodistribution, and metabolite analysis of 11C-PBB3 as a clinically useful PET probe for imaging of tau pathology. J Nucl Med. 2014;55:1532–8.

    Article  CAS  PubMed  Google Scholar 

  81. Kimura Y, Ichise M, Ito H, Shimada H, Ikoma Y, Seki C, et al. PET quantification of tau pathology in human brain with 11C-PBB3. J Nucl Med. 2015;56:1359–65.

    Article  CAS  PubMed  Google Scholar 

  82. Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron. 2013;79:1094–108.

    Article  CAS  PubMed  Google Scholar 

  83. Shao X, Carpenter GM, Desmond TJ, Sherman P, Quesada CA, Fawaz M, et al. Evaluation of [(11)C] N-methyl lansoprazole as a radiopharmaceutical for PET imaging of tau neurofibrillary tangles. ACS Med Chem Lett. 2012;3:936–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Honer M, Gobbi L, Knust H, Kuwabara H, Muri D, Koerner M, et al. Preclinical evaluation of 18F-RO6958948, 11C-RO6931643 and 11C-RO6924963 as novel radiotracers for imaging aggregated tau in AD with positron emission tomography. J Nucl Med. 2018;59:675–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Chen MK, Guilarte TR. Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. Pharmacol Ther. 2008;118:1–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Cagnin A, Kassiou M, Meikle SR, Banati RB. Positron emission tomography imaging of neuroinflammation. Neurotherapeutics. 2007;4:443–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wiley CA, Lopresti BJ, Venneti S, Price J, Klunk WE, DeKosky ST, et al. Carbon 11-labeled Pittsburgh compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol. 2009;66:60–7.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Boutin H, Chauveau F, Thominiaux C, Grégoire MC, James ML, Trebossen R, et al. 11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation. J Nucl Med. 2007;48:573–81.

    Article  CAS  PubMed  Google Scholar 

  90. Van Camp N, Boisgard R, Kuhnast B, Thézé B, Viel T, Grégoire MC, et al. In vivo imaging of neuroinflammation: a comparative study between [(18)F]PBR111, [(11)C]CLINME and [(11)C]PK11195 in an acute rodent model. Eur J Nucl Med Mol Imaging. 2010;37:962–72.

    Article  PubMed  Google Scholar 

  91. Boutin H, Prenant C, Maroy R, Galea J, Greenhalgh AD, Smigova A, et al. [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats. PLoS One. 2013;8:56441.

    Article  CAS  Google Scholar 

  92. Versijpt JJ, Dumont F, Van Laere KJ, Decoo D, Santens P, Audenaert K, et al. Assessment of neuroinflammation and microglial activation in Alzheimer’s disease with radiolabelled PK11195 and single photon emission computed tomography. A pilot study. Eur Neurol. 2003;50:39–47.

    Article  CAS  PubMed  Google Scholar 

  93. Arlicot N, Katsifis A, Garreau L, Mattner F, Vergote J, Duval S, et al. Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation. Eur J Nucl Med Mol Imaging. 2008;35(12):2203–11.

    Article  PubMed  Google Scholar 

  94. Kreisl WC, Lyoo CH, Liow JS, Wei M, Snow J, Page E, et al. (11)C-PBR28 binding to translocator protein increases with progression of Alzheimer’s disease. Neurobiol Aging. 2016;44:53–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Feeney C, Scott G, Raffel J, Roberts S, Coello C, Jolly A, et al. Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain. Eur J Nucl Med Mol Imaging. 2016;43:2201–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ahmad R, Postnov A, Bormans G, Versijpt J, Vandenbulcke M, Van Laere K. Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2016;43:2219–27.

    Article  CAS  PubMed  Google Scholar 

  97. Rodriguez-Vieitez E, Carter SF, Chiotis K, Saint-Aubert L, Leuzy A, Schöll M, et al. Comparison of early-phase 11C-deuterium-l-deprenyl and 11C-Pittsburgh compound B PET for assessing brain perfusion in Alzheimer disease. J Nucl Med. 2016;57:1071–7.

    Article  CAS  PubMed  Google Scholar 

  98. Carter SF, Schöll M, Almkvist O, Wall A, Engler H, Långström B, et al. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-l-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med. 2012;53:37–46.

    Article  CAS  PubMed  Google Scholar 

  99. Esposito G, Giovacchini G, Liow JS, Bhattacharjee AK, Greenstein D, Schapiro M, et al. Imaging neuroinflammation in Alzheimer’s disease with radiolabeled arachidonic acid and PET. J Nucl Med. 2008;49:1414–21.

    Article  CAS  PubMed  Google Scholar 

  100. Rapoport SI. Translational studies on regulation of brain docosahexaenoic acid (DHA) metabolism in vivo. Prostaglandins Leukot Essent Fatty Acids. 2013;88:79–85.

    Article  CAS  PubMed  Google Scholar 

  101. Sun MK, Alkon DL. The ‘memory kinases’: roles of PKC isoforms in signal processing and memory formation. Prog Mol Biol Transl Sci. 2014;122:31–59.

    Article  CAS  PubMed  Google Scholar 

  102. Wang M, Xu L, Gao M, Miller KD, Sledge GW, Zheng QH. [11C] Enzastaurin, the first design and radiosynthesis of a new potential PET agent for imaging of protein kinase C. Bioorg Med Chem Lett. 2011;21:1649–53.

    Article  CAS  PubMed  Google Scholar 

  103. Chiu C, Miller MC, Monahan R, Osgood DP, Stopa EG, Silverberg GD. P-glycoprotein expression and amyloid accumulation in human aging and Alzheimer’s disease: preliminary observations. Neurobiol Aging. 2015;36:2475–82.

    Article  CAS  PubMed  Google Scholar 

  104. Shimada H, Hirano S, Sinotoh H, Ota T, Tanaka N, Sato K, et al. Dementia with Lewy bodies can be well-differentiated from Alzheimer’s disease by measurement of brain acetylcholinesterase activity-a [11C]MP4A PET study. Int J Geriatr Psychiatry. 2015;30:1105–13.

    Article  CAS  PubMed  Google Scholar 

  105. Kasuya M, Meguro K, Okamura N, Funaki Y, Ishikawa H, Tanaka N, et al. Greater responsiveness to donepezil in Alzheimer patients with higher levels of acetylcholinesterase based on attention task scores and a donepezil PET study. Alzheimer Dis Assoc Disord. 2012;26:113–8.

    Article  CAS  PubMed  Google Scholar 

  106. Fernández S, Giglio J, Reyes AL, Damián A, Pérez C, Pérez DI, et al. 3-(Benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole: a PET radiotracer to measure acetylcholinesterase in brain. Future Med Chem. 2017;9:983–94.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Nuclear Medicine Department, University Hospital of Larissa, Mezourlo, 41110, Larissa, Thessaly, Greece

    Varvara Valotassiou, Ioannis Tsougos, Dimitrios Psimadas, Sotiria Alexiou & Panagiotis Georgoulias

  2. Medical Physics, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Julia Malamitsi

  3. IASIS Community Medical Center for the Elderly, Athens, Greece

    John Papatriantafyllou

  4. Neurology Department, University Hospital of Larissa, Thessaly, Greece

    Efthimios Dardiotis & George Hadjigeorgiou

  5. Department of Neurology, Medical School, University of Cyprus, Nicosia, Greece

    George Hadjigeorgiou

Authors
  1. Varvara Valotassiou
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  2. Julia Malamitsi
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  3. John Papatriantafyllou
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  4. Efthimios Dardiotis
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  9. Panagiotis Georgoulias
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Correspondence to Varvara Valotassiou.

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Valotassiou, V., Malamitsi, J., Papatriantafyllou, J. et al. SPECT and PET imaging in Alzheimer’s disease. Ann Nucl Med 32, 583–593 (2018). https://doi.org/10.1007/s12149-018-1292-6

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  • DOI: https://doi.org/10.1007/s12149-018-1292-6

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