Skip to main content
SpringerLink
Log in

PET Imaging of Translocator Protein Expression in Neurological Disorders

  • Chapter
  • First Online:
Book cover PET and SPECT of Neurobiological Systems

  • 2182 Accesses

Abstract

Microglia provide the intrinsic immune defence of the brain and are activated by any injurious process. As such they provide a nonspecific marker of disease activity. Their function can be both detrimental and beneficial as they release cytokines which can drive disease progression but also release restorative growth factors, can help clear cellular debris and abnormal protein aggregations and can remodel connections as an adaptive response to brain damage. Activated microglia express translocator protein (TSPO), and this allows them to be imaged in vivo with positron emission tomography (PET) radioligands which are substrates. In this chapter, the role of TSPO imaging with PET is discussed in neurodegenerative and inflammatory brain diseases and in focal brain injury due to trauma or stroke.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 309.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 399.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

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

    Article  PubMed  Google Scholar 

  • Andrews TC, Weeks RA, Turjanski N, Gunn RN, Watkins LHA, Sahakian B, Hodges JR, Rosser AE, Wood NW, Brooks DJ (1999) Huntington’s disease progression PET and clinical observations. Brain 122:2353–2363

    Article  PubMed  Google Scholar 

  • Banati RB (2002a) Brain plasticity and microglia: is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation? J Physiol Paris 96:289–299

    Article  PubMed  Google Scholar 

  • Banati RB (2002b) Visualising microglial activation in vivo. Glia 40:206–217

    Article  PubMed  Google Scholar 

  • Banati RB, Myers R, Kreutzberg GW (1997) 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 26:77–82

    Article  CAS  PubMed  Google Scholar 

  • Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, Price G, Wegner F, Giovannoni G, Miller DH, Perkin GD, Smith T, Hewson AK, Bydder G, Kreutzberg GW, Jones T, Cuzner ML, Myers R (2000) The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 123(Pt 11):2321–2337

    Article  PubMed  Google Scholar 

  • Benveniste EN (2007) Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Molecular Medicine 75:165–173

    Article  Google Scholar 

  • Boche D, Perry VH, Nicoll JA (2013) Activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol 39(1):3–18

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Braak E (1997) Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 18:351–357

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134

    Article  PubMed  Google Scholar 

  • Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB (2001) In-vivo measurement of activated microglia in dementia. Lancet 358:461–467

    Article  CAS  PubMed  Google Scholar 

  • Cagnin A, Rossor M, Sampson EL, Mackinnon T, Banati RB (2004) In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol 56:894–897

    Article  PubMed  Google Scholar 

  • Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517

    Article  CAS  PubMed  Google Scholar 

  • Confavreux C, Vukusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430–1438

    Article  CAS  PubMed  Google Scholar 

  • De Groot CJ, Bergers E, Kamphorst W, Ravid R, Polman CH, Barkhof F, van der Valk P (2001) Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and (p)reactive lesions. Brain 124:1635–1645

    Article  PubMed  Google Scholar 

  • Debruyne JC, Versijpt J, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, Achten E, Slegers G, Dierckx RA, Korf J, De Reuck JL (2003) PET visualization of microglia in multiple sclerosis patients using [11C]PK11195. Eur J Neurol 10:257–264

    Article  CAS  PubMed  Google Scholar 

  • Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56:321–339

    Article  CAS  PubMed  Google Scholar 

  • Dodel R, Spottke A, Gerhard A, Reuss A, Reinecker S, Schimke N, Trenkwalder C, Sixel-Doring F, Herting B, Kamm C, Gasser T, Sawires M, Geser F, Kollensperger M, Seppi K, Kloss M, Krause M, Daniels C, Deuschl G, Bottger S, Naumann M, Lipp A, Gruber D, Kupsch A, Du Y, Turkheimer F, Brooks DJ, Klockgether T, Poewe W, Wenning G, Schade-Brittinger C, Oertel WH, Eggert K (2010) Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial). Mov Disord 25:97–107

    Article  PubMed  Google Scholar 

  • Dolle F, Luus C, Reynolds A, Kassiou M (2009) Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography. Curr Med Chem 16:2899–2923

    Article  CAS  PubMed  Google Scholar 

  • Doorduin J, de Vries EF, Dierckx RA, Klein HC (2008) PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders. Curr Pharm Des 14:3297–3315

    Article  CAS  PubMed  Google Scholar 

  • Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC (2009) Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med 50:1801–1807

    Article  PubMed  Google Scholar 

  • Edison P, Archer H, Hinz R, Fox N, Kennedy A, Rossor M, Brooks DJ (2007a) Relationship between the distribution of microglial activation and amyloid deposition in Alzheimer’s disease: an 11C-PK11195 and 11C-PIB PET study. J Neurol Neurosurg Psychiatry 78:219–219

    Google Scholar 

  • Edison P, Archer HA, Hinz R, Hammers A, Pavese N, Tai YF, Hotton G, Cutler D, Fox N, Kennedy A, Rossor M, Brooks DJ (2007b) Amyloid, hypometabolism, and cognition in Alzheimer disease – an [11C]PIB and [18F]FDG PET study. Neurology 68:501–508

    Article  CAS  PubMed  Google Scholar 

  • Gerhard A, Banati RB, Goerres GB, Cagnin A, Myers R, Gunn RN, Turkheimer F, Good CD, Mathias CJ, Quinn N, Schwarz J, Brooks DJ (2003) [(11)C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology 61:686–689

    Article  CAS  PubMed  Google Scholar 

  • Gerhard A, Schwarz J, Myers R, Wise R, Banati RB (2005) Evolution of microglial activation in patients after ischemic stroke: a [(11)C](R)-PK11195 PET study. Neuroimage 24:591–595

    Article  PubMed  Google Scholar 

  • Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, Eggert K, Oertel W, Banati RB, Brooks DJ (2006a) In vivo imaging of microglial activation with [(11)C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis 21:404–412

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394

    Article  CAS  PubMed  Google Scholar 

  • Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2003) Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol 106:518–526

    Article  CAS  PubMed  Google Scholar 

  • Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318

    Article  CAS  PubMed  Google Scholar 

  • Magliozzi R, Howell OW, Reeves C, Roncaroli F, Nicholas R, Serafini B, Aloisi F, Reynolds R (2010) A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 68:477–493

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Oh U, Fujita M, Ikonomidou VN, Evangelou IE, Matsuura E, Harberts E, Ohayon J, Pike VW, Zhang Y, Zoghbi SS, Innis RB, Jacobson S (2011) Translocator protein PET imaging for glial activation in multiple sclerosis. J Neuroimmune Pharmacol 6(3):354–361

    Article  PubMed Central  PubMed  Google Scholar 

  • Okello A, Edison P, Archer HA, Turkheimer FE, Kennedy J, Bullock R, Walker Z, Kennedy A, Fox N, Rossor M, Brooks DJ (2009) Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 72:56–62

    Article  CAS  PubMed  Google Scholar 

  • Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T (2005) Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol 57:168–175

    Article  CAS  PubMed  Google Scholar 

  • Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, Rhodes C, Pulford DJ, Bennacef I, Parker CA, StJean PL, Cardon LR, Mooser VE, Matthews PM, Rabiner EA, Rubio JP (2012) An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab 32:1–5

    Article  CAS  PubMed  Google Scholar 

  • Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapere JJ, Lindemann P, Norenberg MD, Nutt D, Weizman A, Zhang MR, Gavish M (2006) Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci 27:402–409

    Article  CAS  PubMed  Google Scholar 

  • Pavese N, Gerhard A, Tai YF, Ho AK, Turkheimer F, Barker RA, Brooks DJ, Piccini P (2006) Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 66:1638–1643

    Article  CAS  PubMed  Google Scholar 

  • Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985–1992

    Article  CAS  PubMed  Google Scholar 

  • Peterson JW, Bo L, Mork S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400

    Article  CAS  PubMed  Google Scholar 

  • Politis M, Pavese N, Tai YF, Kiferle L, Mason SL, Brooks DJ, Tabrizi SJ, Barker RA, Piccini P (2011) Microglial activation in regions related to cognitive function predicts disease onset in Huntington’s disease: a multimodal imaging study. Hum Brain Mapp 32:258–270

    Article  PubMed  Google Scholar 

  • Politis M, Giannetti P, Su P, Turkheimer F, Keihaninejad S, Wu K, Waldman A, Malik O, Matthews PM, Reynolds R, Nicholas R, Piccini P (2012) Increased PK11195 PET binding in the cortex of patients with MS correlates with disability. Neurology 79(6):523–530

    Article  PubMed  Google Scholar 

  • Ramlackhansingh AF, Brooks DJ, Greenwood RJ, Bose SK, Turkheimer FE, Kinnunen KM, Gentleman S, Heckemann RA, Gunanayagam K, Gelosa G, Sharp DJ (2011) Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol 70(3):374–383

    Article  PubMed  Google Scholar 

  • Ransohoff RM, Perry VH (2009) Microglial physiology: unique stimuli, specialized responses. Ann Rev Immunol 27:119–145

    Article  CAS  Google Scholar 

  • Sapp E, Schwarz C, Chase K, Bhide PG, Young AB, Penney J, Vonsattel JP, Aronin N, Difiglia M (1997) Huntingtin localization in brains of normal and Huntington’s disease patients. Ann Neurol 42:604–612

    Article  CAS  PubMed  Google Scholar 

  • Sapp E, Kegel KB, Aronin N, Hashikawa T, Uchiyama Y, Tohyama K, Bhide PG, Vonsattel JP, DiFiglia M (2001) Early and progressive accumulation of reactive microglia in the Huntington disease brain. J Neuropathol Exp Neurol 60:161–172

    CAS  PubMed  Google Scholar 

  • Schapira AH, Olanow CW (2004) Neuroprotection in Parkinson disease: mysteries, myths, and misconceptions. JAMA 291:358–364

    Article  CAS  PubMed  Google Scholar 

  • Schuitemaker A, Kropholler MA, Boellaard R, van der Flier WM, Kloet RW, van der Doef TF, Knol DL, Windhorst AD, Luurtsema G, Barkhof F, Jonker C, Lammertsma AA, Scheltens P, van Berckel BN (2013) Microglial activation in Alzheimer’s disease: an (R)-[(1)(1)C]PK11195 positron emission tomography study. Neurobiol Aging 34:128–136

    Article  CAS  PubMed  Google Scholar 

  • Simpson BS, Pavese N, Ramlackhansingh AF, Breen DP, Barker RA, Brooks DJ (2012) Clinical correlates of brain inflammation in Parkinson’s disease: a PET study. Mov Disord 27:775

    Article  Google Scholar 

  • Stefanova N, Reindl M, Neumann M, Kahle PJ, Poewe W, Wenning GK (2007) Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. Mov Disord 22:2196–2203

    Article  PubMed  Google Scholar 

  • Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, Piccini P (2007) Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain 130:1759–1766

    Article  PubMed  Google Scholar 

  • Turner MR, Cagnin A, Turkheimer FE, Miller CC, Shaw CE, Brooks DJ, Leigh PN, Banati RB (2004) Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis 15:601–609

    Article  CAS  PubMed  Google Scholar 

  • van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, Luurtsema G, Windhorst AD, Cahn W, Lammertsma AA, Kahn RS (2008) Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry 64:820–822

    Article  PubMed  Google Scholar 

  • Varnum MM, Ikezu T (2012) The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain. Arch Immunol Ther Exp (Warsz) 60:251–266

    Article  CAS  Google Scholar 

  • Versijpt J, Debruyne JC, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, Achten E, Slegers G, Dierckx RA, Korf J, De Reuck JL (2005) Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study. Mult Scler 11:127–134

    Article  CAS  PubMed  Google Scholar 

  • Yasuno F, Ota M, Kosaka J, Ito H, Higuchi M, Doronbekov TK, Nozaki S, Fujimura Y, Koeda M, Asada T, Suhara T (2008) Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry 64:835–841

    Article  CAS  PubMed  Google Scholar 

  • Yasuno F, Kosaka J, Ota M, Higuchi M, Ito H, Fujimura Y, Nozaki S, Takahashi S, Mizukami K, Asada T, Suhara T (2012) Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [(11)C]DAA1106. Psychiatry Res 203:67–74

    Article  CAS  PubMed  Google Scholar 

  • Yokokura M, Mori N, Yagi S, Yoshikawa E, Kikuchi M, Yoshihara Y, Wakuda T, Sugihara G, Takebayashi K, Suda S, Iwata Y, Ueki T, Tsuchiya KJ, Suzuki K, Nakamura K, Ouchi Y (2011) In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 38:343–351

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Imperial College London, London, UK

    David J. Brooks

  2. Department of Nuclear Medicine, Aarhus University, Aarhus, Denmark

    David J. Brooks

Authors
  1. David J. Brooks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J. Brooks .

Editor information

Editors and Affiliations

  1. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Rudi A.J.O. Dierckx

  2. Faculty of Electrical Engineering and Information Technology, University of Applied Sciences Offenburg, Offenburg, Germany

    Andreas Otte

  3. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Erik F.J. de Vries

  4. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Aren van Waarde

  5. Molecular Neurobiology, Universtiy of Groningen, Groningen, The Netherlands

    Paul G.M. Luiten

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Brooks, D.J. (2014). PET Imaging of Translocator Protein Expression in Neurological Disorders. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Luiten, P. (eds) PET and SPECT of Neurobiological Systems. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-42014-6_22

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-42014-6_22

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-42013-9

  • Online ISBN: 978-3-642-42014-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation