Skip to main content

Advertisement

SpringerLink
Log in

Perspectives in TSPO PET Imaging for Neurologic Diseases

  • Perspective
  • Published:
Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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.

    Article  CAS  Google Scholar 

  2. Casellas P, Galiegue S, Basile AS. Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int. 2002;40:475–86.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  9. Stefaniak J, O’Brien J. Imaging of neuroinflammation in dementia: a review. J Neurol Neurosurg Psychiatry. 2016;87:21–8.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  13. Cagnin A, Rossor M, Sampson EL, et al. In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol. 2004;56:894–7.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  18. Koshimori Y, Ko JH, Mizrahi R, et al. Imaging striatal microglial activation in patients with Parkinson’s disease. PLoS One. 2015;10:e0138721.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  22. Block F, Dihne M, Loos M. Inflammation in areas of remote changes following focal brain lesion. Prog Neurobiol. 2005;75:342–65.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

Download references

Funding

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

Author information

Authors and Affiliations

  1. Seoul National University Bundang Hospital, Seongnam, South Korea

    Yoo Sung Song

Authors
  1. Yoo Sung Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoo Sung Song.

Ethics declarations

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.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, Y.S. Perspectives in TSPO PET Imaging for Neurologic Diseases. Nucl Med Mol Imaging 53, 382–385 (2019). https://doi.org/10.1007/s13139-019-00620-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13139-019-00620-y

Keywords

Search

Navigation