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Nuclear Medicine and Molecular Imaging

, Volume 53, Issue 6, pp 382–385 | Cite as

Perspectives in TSPO PET Imaging for Neurologic Diseases

  • Yoo Sung SongEmail author
Perspective
  • 28 Downloads

Abstract

The translocator protein (18 kDa) (TSPO) is a mitochondrial transmembrane protein, which has brought attention as a neuroinflammatory biomarker. Positron emission tomography (PET) imaging studies have been done for several decades, since neuroinflammation has been implicated as an important pathophysiology of several common neurologic disorders. However, despite numerous previous studies with positive findings, its clinical significance is not yet clear. Various attempts to overcome the limitations are ongoing, in order to bring acceptance for use in clinics.

Keywords

Neuroinflammation Neurologic disease Positron emission tomography Translocator protein (18 kDa) 

Notes

Funding Information

This work was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) (grant no. 2016R1D1A1A02937028).

Compliance With Ethical Standards

Conflict of Interest

This work was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) (no. 2016R1D1A1A02937028).

Ethical Approval

This article does not contain any studies with human participants or animals performed by the author.

Informed consent

Not applicable.

References

  1. 1.
    Papadopoulos V, Baraldi M, Guilarte TR, et al. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci. 2006;27:402–9.CrossRefGoogle Scholar
  2. 2.
    Casellas P, Galiegue S, Basile AS. Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int. 2002;40:475–86.CrossRefGoogle Scholar
  3. 3.
    Maezawa I, Zimin PI, Wulff H, Jin LW. Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity. J Biol Chem. 2011;286:3693–706.CrossRefGoogle Scholar
  4. 4.
    Morales I, Jimenez JM, Mancilla M, Maccioni RB. Tau oligomers and fibrils induce activation of microglial cells. J Alzheimers Dis. 2013;37:849–56.CrossRefGoogle Scholar
  5. 5.
    Edison P, Archer HA, Gerhard A, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32:412–9.CrossRefGoogle Scholar
  6. 6.
    Yokokura M, Mori N, Yagi S, 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.CrossRefGoogle Scholar
  7. 7.
    Wiley CA, Lopresti BJ, Venneti S, 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.CrossRefGoogle Scholar
  8. 8.
    Schuitemaker A, Kropholler MA, Boellaard R, et al. Microglial activation in Alzheimer’s disease: an (R)-[11C]PK11195 positron emission tomography study. Neurobiol Aging. 2013;34:128–36.CrossRefGoogle Scholar
  9. 9.
    Stefaniak J, O’Brien J. Imaging of neuroinflammation in dementia: a review. J Neurol Neurosurg Psychiatry. 2016;87:21–8.CrossRefGoogle Scholar
  10. 10.
    Carter SF, Scholl M, Almkvist O, 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.CrossRefGoogle Scholar
  11. 11.
    Kreisl WC, Lyoo CH, McGwier M, et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease. Brain. 2013;136:2228–38.CrossRefGoogle Scholar
  12. 12.
    Iannaccone S, Cerami C, Alessio M, et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord. 2013;19:47–52.CrossRefGoogle Scholar
  13. 13.
    Cagnin A, Rossor M, Sampson EL, et al. In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol. 2004;56:894–7.CrossRefGoogle Scholar
  14. 14.
    Gerhard A, Watts J, Trender-Gerhard I, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration. Mov Disord. 2004;19:1221–6.CrossRefGoogle Scholar
  15. 15.
    Gerhard A, Trender-Gerhard I, Turkheimer F, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive supranuclear palsy. Mov Disord. 2006;21:89–93.CrossRefGoogle Scholar
  16. 16.
    Gerhard A, Banati RB, Goerres GB, et al. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology. 2003;61:686–9.CrossRefGoogle Scholar
  17. 17.
    Dodel R, Spottke A, Gerhard A, et al. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [11C] (R)-PK11195 PET (MEMSA-trial). Mov Disord. 2010;25:97–107.CrossRefGoogle Scholar
  18. 18.
    Koshimori Y, Ko JH, Mizrahi R, et al. Imaging striatal microglial activation in patients with Parkinson’s disease. PLoS One. 2015;10:e0138721.CrossRefGoogle Scholar
  19. 19.
    Gulyas B, Toth M, Schain M, et al. Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: a PET study with the TSPO molecular imaging biomarker [11C]vinpocetine. J Neurol Sci. 2012;320:110–7.CrossRefGoogle Scholar
  20. 20.
    Thiel A, Radlinska BA, Paquette C, et al. The temporal dynamics of poststroke neuroinflammation: a longitudinal diffusion tensor imaging-guided PET study with 11C-PK11195 in acute subcortical stroke. J Nucl Med. 2010;51:1404–12.CrossRefGoogle Scholar
  21. 21.
    Gulyas B, Toth M, Vas A, et al. Visualising neuroinflammation in post-stroke patients: a comparative PET study with the TSPO molecular imaging biomarkers [11C]PK11195 and [11C]vinpocetine. Curr Radiopharm. 2012;5:19–28.CrossRefGoogle Scholar
  22. 22.
    Block F, Dihne M, Loos M. Inflammation in areas of remote changes following focal brain lesion. Prog Neurobiol. 2005;75:342–65.CrossRefGoogle Scholar
  23. 23.
    Owen DR, Yeo AJ, Gunn RN, 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.CrossRefGoogle Scholar
  24. 24.
    Murail S, Robert JC, Coic YM, et al. Secondary and tertiary structures of the transmembrane domains of the translocator protein TSPO determined by NMR. Stabilization of the TSPO tertiary fold upon ligand binding. Biochim Biophys Acta. 1778;2008:1375–81.Google Scholar
  25. 25.
    Li F, Liu J, Zheng Y, et al. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science. 2015;347:555–8.CrossRefGoogle Scholar
  26. 26.
    Tiwari AK, Ji B, Yui J, et al. [18F]FEBMP: positron emission tomography imaging of TSPO in a model of neuroinflammation in rats, and in vitro autoradiograms of the human brain. Theranostics. 2015;5:961–9.CrossRefGoogle Scholar
  27. 27.
    Fan Z, Calsolaro V, Atkinson RA, et al. Flutriciclamide (18F-GE180) PET: first-in-human PET study of novel third-generation in vivo marker of human translocator protein. J Nucl Med. 2016;57:1753–9.CrossRefGoogle Scholar
  28. 28.
    Colasanti A, Owen DR, Grozeva D, et al. Bipolar disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa translocator protein (TSPO). Psychoneuroendocrinology. 2013;38:2826–9.CrossRefGoogle Scholar
  29. 29.
    Nakamura K, Yamada K, Iwayama Y, et al. Evidence that variation in the peripheral benzodiazepine receptor (PBR) gene influences susceptibility to panic disorder. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:222–6.CrossRefGoogle Scholar
  30. 30.
    Lockhart A, Davis B, Matthews JC, et al. The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant alpha1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker. Nucl Med Biol. 2003;30:199–206.CrossRefGoogle Scholar
  31. 31.
    Turkheimer FE, Rizzo G, Bloomfield PS, et al. The methodology of TSPO imaging with positron emission tomography. Biochem Soc Trans. 2015;43:586–92.CrossRefGoogle Scholar
  32. 32.
    Rizzo G, Veronese M, Tonietto M, et al. Kinetic modeling without accounting for the vascular component impairs the quantification of [11C]PBR28 brain PET data. J Cereb Blood Flow Metab. 2014;34:1060–9.CrossRefGoogle Scholar
  33. 33.
    Owen DR, Guo Q, Rabiner EA, Gunn RN. The impact of the rs6971 polymorphism in TSPO for quantification and study design. Clin Transl Imaging 2015;3:417–22.CrossRefGoogle Scholar
  34. 34.
    Lyoo CH, Ikawa M, Liow JS, et al. Cerebellum can serve as a pseudo-reference region in Alzheimer disease to detect neuroinflammation measured with PET radioligand binding to translocator protein. J Nucl Med. 2015;56:701–6.CrossRefGoogle Scholar
  35. 35.
    Moon BS, Kim BS, Park C, et al. [18F]Fluoromethyl-PBR28 as a potential radiotracer for TSPO: preclinical comparison with [11C]PBR28 in a rat model of neuroinflammation. Bioconjug Chem. 2014;25:442–50.CrossRefGoogle Scholar

Copyright information

© Korean Society of Nuclear Medicine 2019

Authors and Affiliations

  1. 1.Seoul National University Bundang HospitalSeongnamSouth Korea

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