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PET Imaging in Neuroinflammation

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Inflammation in Parkinson's Disease

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Abstract

The presence of microglial activation in the brain provides a marker of disease activity. The function of activated microglia can be both detrimental and beneficial depending on the phenotype. Microglia with the M1 phenotype release cytokines, which may drive disease progression, while M2 microglia generate restorative growth factors, help clear cellular debris and abnormal protein aggregations, and remodel connections as an adaptive response to brain damage. Activated microglia express translocator protein and cannabinoid CB2 sites, which allows their presence to be imaged in vivo with positron emission tomography radioligands. In this chapter, the role of microglial imaging is discussed in Parkinsonian disorders and other neurodegenerative and inflammatory brain diseases.

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References

  1. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996;19:312–8.

    Article  CAS  PubMed  Google Scholar 

  2. Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009;27:119–45.

    Article  CAS  PubMed  Google Scholar 

  3. Varnum MM, Ikezu T. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain. Arch Immunol Ther Exp (Warsz). 2012;60:251–66.

    Article  CAS  Google Scholar 

  4. Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapere JJ, Lindemann P, et al. Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci. 2006;27:402–9.

    Article  CAS  PubMed  Google Scholar 

  5. Banati RB. Visualising microglial activation in vivo. Glia. 2002;40:206–17.

    Article  PubMed  Google Scholar 

  6. Doorduin J, de Vries EF, Dierckx RA, Klein HC. PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders. Curr Pharm Des. 2008;14:3297–315.

    Article  CAS  PubMed  Google Scholar 

  7. Dolle F, Luus C, Reynolds A, Kassiou M. Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography. Curr Med Chem. 2009;16:2899–923.

    Article  CAS  PubMed  Google Scholar 

  8. Banati RB, Myers R, Kreutzberg GW. PK (‘peripheral benzodiazepine’)–binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to activated microglia. J Neurocytol. 1997;26:77–82.

    Article  CAS  PubMed  Google Scholar 

  9. Banati RB. Brain plasticity and microglia: is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation? J Physiol Paris. 2002;96:289–99.

    Article  PubMed  Google Scholar 

  10. Anderson AN, Pavese N, Edison P, Tai YF, Hammers A, Gerhard A, et al. A systematic comparison of kinetic modelling methods generating parametric maps for [(11)C]-(R)-PK11195. Neuroimage. 2007;36:28–37.

    Article  PubMed  Google Scholar 

  11. Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012;32:1–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res. 2004;318:121–34.

    Article  PubMed  Google Scholar 

  13. McGeer P, Kawamata T, Walker DG, Akiyama H, Tooyama I, McGeer EG. Microglia in degenerative disease. Glia. 1993;7:84–92.

    Article  CAS  PubMed  Google Scholar 

  14. Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol. 2003;106:518–26.

    Article  CAS  PubMed  Google Scholar 

  15. Vingerhoets FJG, Snow BJ, Langston JW, Tetrud JM, Schulzer M, Calne DB. Positron emission tomographic evidence for progression of human MPTP-induced dopaminergic lesions. Ann Neurol. 1994;36:765–70.

    Article  CAS  PubMed  Google Scholar 

  16. Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol. 1999;46:598–605.

    Article  CAS  PubMed  Google Scholar 

  17. Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, et al. Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol. 2005;57:168–75.

    Article  CAS  PubMed  Google Scholar 

  18. Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, et al. In vivo imaging of microglial activation with [(11)C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis. 2006;21:404–12.

    Article  CAS  PubMed  Google Scholar 

  19. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23:837–44.

    Article  PubMed  Google Scholar 

  20. Edison P, Rowe CC, Rinne J, Ahmed I, Villemagne VL, Ng S, et al. Amyloid load in Lewy body dementia (LBD), Parkinson’s disease dementia (PDD) and Parkinson’s disease (PD) measured with C-11-PIB PET. Neurology. 2007;68:A98–A.

    Google Scholar 

  21. Simpson BS, Pavese N, Ramlackhansingh AF, Breen DP, Barker RA, Brooks DJ. Clinical correlates of brain inflammation in Parkinson’s disease: A PET study. Mov Disord. 2012;27 Suppl 1:775.

    Google Scholar 

  22. Ishizawa K, Komori T, Sasaki S, Arai N, Mizutani T, Hirose T. Microglial activation parallels system degeneration in multiple system atrophy. J Neuropathol Exp Neurol. 2004;63:43–52.

    PubMed  Google Scholar 

  23. Gerhard A, Banati RB, Goerres GB, Cagnin A, Myers R, Gunn RN, et al. [(11)C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology. 2003;61:686–9.

    Article  CAS  PubMed  Google Scholar 

  24. Stefanova N, Reindl M, Neumann M, Kahle PJ, Poewe W, Wenning GK. Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. Mov Disord. 2007;22:2196–203.

    Article  PubMed  Google Scholar 

  25. Dodel R, Spottke A, Gerhard A, Reuss A, Reinecker S, Schimke N, et al. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial). Mov Disord. 2010;25:97–107.

    Article  PubMed  Google Scholar 

  26. Ishizawa K, Dickson DW. Microglial activation parallels system degeneration in progressive supranuclear palsy and corticobasal degeneration. J Neuropathol Exp Neurol. 2001;60:647–57.

    CAS  PubMed  Google Scholar 

  27. Gerhard A, Trender-Gerhard I, Turkheimer F, Quinn NP, Bhatia KP, Brooks DJ. In vivo imaging of microglial activation with [(11)C](R)-PK11195 PET in progressive supranuclear palsy. Mov Disord. 2006;21:89–93.

    Article  PubMed  Google Scholar 

  28. Dickson DW. The pathogenesis of senile plaques. J Neuropathol Exp Neurol. 1997;56:321–39.

    Article  CAS  PubMed  Google Scholar 

  29. 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 

  30. Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, et al. In-vivo measurement of activated microglia in dementia. Lancet. 2001;358:461–7.

    Article  CAS  PubMed  Google Scholar 

  31. Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: An [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32:412–9.

    Article  CAS  PubMed  Google Scholar 

  32. Yasuno F, Ota M, Kosaka J, Ito H, Higuchi M, Doronbekov TK, et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry. 2008;64:835–41.

    Article  CAS  PubMed  Google Scholar 

  33. Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, Hammers A, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: An [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32(3):412–9.

    Article  CAS  PubMed  Google Scholar 

  34. Yokokura M, Mori N, Yagi S, Yoshikawa E, Kikuchi M, Yoshihara Y, et al. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2011;38:343–51.

    Article  CAS  PubMed  Google Scholar 

  35. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Arch Neurol. 2001;58:1985–92.

    Article  CAS  PubMed  Google Scholar 

  36. Okello A, Edison P, Archer HA, Turkheimer FE, Kennedy J, Bullock R, et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology. 2009;72:56–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Yasuno F, Kosaka J, Ota M, Higuchi M, Ito H, Fujimura Y, et al. Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [(11)C]DAA1106. Psychiatry Res. 2012;203:67–74.

    Article  CAS  PubMed  Google Scholar 

  38. Cagnin A, Rossor M, Sampson EL, Mackinnon T, Banati RB. In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol. 2004;56:894–7.

    Article  PubMed  Google Scholar 

  39. Turner MR, Cagnin A, Turkheimer FE, Miller CC, Shaw CE, Brooks DJ, et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis. 2004;15:601–9.

    Article  CAS  PubMed  Google Scholar 

  40. Sapp E, Schwarz C, Chase K, Bhide PG, Young AB, Penney J, et al. Huntingtin localization in brains of normal and Huntington’s disease patients. Ann Neurol. 1997;42:604–12.

    Article  CAS  PubMed  Google Scholar 

  41. Andrews TC, Weeks RA, Turjanski N, Gunn RN, Watkins LHA, Sahakian B, et al. Huntington’s disease progression PET and clinical observations. Brain. 1999;122:2353–63.

    Article  PubMed  Google Scholar 

  42. Sapp E, Kegel KB, Aronin N, Hashikawa T, Uchiyama Y, Tohyama K, et al. Early and progressive accumulation of reactive microglia in the Huntington disease brain. J Neuropathol Exp Neurol. 2001;60:161–72.

    CAS  PubMed  Google Scholar 

  43. Pavese N, Gerhard A, Tai YF, Ho AK, Turkheimer F, Barker RA, et al. Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology. 2006;66:1638–43.

    Article  CAS  PubMed  Google Scholar 

  44. Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, et al. Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain. 2007;130:1759–66.

    Article  PubMed  Google Scholar 

  45. Politis M, Pavese N, Tai YF, Kiferle L, Mason SL, Brooks DJ, et al. Microglial activation in regions related to cognitive function predicts disease onset in Huntington’s disease: a multimodal imaging study. Hum Brain Mapp. 2011;32:258–70.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Imperial College London, London, UK

    David J. Brooks M.D., D.Sc., F.R.C.P. (UK)

  2. Aarhus University, Aarhus, Denmark

    David J. Brooks M.D., D.Sc., F.R.C.P. (UK)

  3. Medicine ICL, Nuclear Medicine AU, Hammersmith Hospital, London, UK

    David J. Brooks M.D., D.Sc., F.R.C.P. (UK)

Authors
  1. David J. Brooks M.D., D.Sc., F.R.C.P. (UK)
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Editors and Affiliations

  1. North Texas Movement Disorders Institute, Inc., Bedford, Texas, USA

    Madhavi Thomas

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© 2014 Springer International Publishing Switzerland

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Brooks, D.J. (2014). PET Imaging in Neuroinflammation. In: Thomas, M. (eds) Inflammation in Parkinson's Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-08046-8_9

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  • DOI: https://doi.org/10.1007/978-3-319-08046-8_9

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-08045-1

  • Online ISBN: 978-3-319-08046-8

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