The validity of 18F-GE180 as a TSPO imaging agent

  • Paolo Zanotti-FregonaraEmail author
  • Mattia Veronese
  • Belen Pascual
  • Robert C. Rostomily
  • Federico Turkheimer
  • Joseph C. Masdeu
Letter to the Editor

Dear Sir,

To image the 18-kDa mitochondrial translocator protein (TSPO), a putative biomarker for inflammation, dozens of PET radioligands have been synthesized over the years [1]. None of them, however, presents optimal imaging characteristics. A drawback common to most, if not all, TSPO ligands is that they are sensitive to a single-aminoacid polymorphism of the target protein [2]. This polymorphism differentiates subjects into high- (HAB), mixed- (MAB), and low- (LAB) affinity binders.

Therefore, a TSPO ligand providing better imaging quality is still a much sought-after goal. 18F-GE180 is a novel tricyclic indole compound that binds to TSPO with high affinity [3], and has been used with satisfactory results in a variety of preclinical models [4, 5, 6]. Head-to-head comparisons in animal models of neuroinflammation showed 18F-GE180 to have better imaging properties than 11C-(R)-PK11195 [4] and 18F-DPA-714 [6], although it seemed to be less sensitive than 11C-DPA-713 [5].



Compliance with ethical standards

Conflict of interest

The authors declare they have no conflict of interest.

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


  1. 1.
    Cumming P, Burgher B, Patkar O, et al. Sifting through the surfeit of neuroinflammation tracers. J Cereb Blood Flow Metab. 2018;38:204–24.CrossRefGoogle Scholar
  2. 2.
    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
  3. 3.
    Wadsworth H, Jones PA, Chau WF, et al. [(1)(8)F]GE-180: a novel fluorine-18 labelled PET tracer for imaging translocator protein 18 kDa (TSPO). Bioorg Med Chem Lett. 2012;22:1308–13.CrossRefGoogle Scholar
  4. 4.
    Boutin H, Murray K, Pradillo J, et al. 18F-GE-180: a novel TSPO radiotracer compared to 11C-R-PK11195 in a preclinical model of stroke. Eur J Nucl Med Mol Imaging. 2015;42:503–11.CrossRefGoogle Scholar
  5. 5.
    Chaney A, Cropper HC, Johnson EM, et al. (11)C-DPA-713 versus (18)F-GE-180: a preclinical comparison of TSPO-PET tracers to visualize acute and chronic neuroinflammation in a mouse model of ischemic stroke. J Nucl Med. 2018;60(1):122–28.Google Scholar
  6. 6.
    Sridharan S, Lepelletier FX, Trigg W, et al. Comparative evaluation of three TSPO PET radiotracers in a LPS-induced model of mild neuroinflammation in rats. Mol Imaging Biol. 2017;19:77–89.CrossRefGoogle Scholar
  7. 7.
    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
  8. 8.
    Feeney C, Scott G, Raffel J, 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.CrossRefGoogle Scholar
  9. 9.
    Zanotti-Fregonara P, Pascual B, Rizzo G, et al. Head-to-head comparison of (11)C-PBR28 and (18)F-GE180 for quantification of the translocator protein in the human brain. J Nucl Med. 2018;59:1260–6.CrossRefGoogle Scholar
  10. 10.
    Albert NL, Unterrainer M, Fleischmann DF, et al. TSPO PET for glioma imaging using the novel ligand 18F-GE-180: first results in patients with glioblastoma. Eur J Nucl Med Mol Imaging. 2017;44(13):2230–238.Google Scholar
  11. 11.
    Unterrainer M, Fleischmann DF, Diekmann C, et al. Comparison of (18)F-GE-180 and dynamic (18)F-FET PET in high grade glioma: a double-tracer pilot study. Eur J Nucl Med Mol Imaging. 2018 Sep 22 [Epub ahead of print].Google Scholar
  12. 12.
    Unterrainer M, Mahler C, Vomacka L, et al. TSPO PET with [(18)F]GE-180 sensitively detects focal neuroinflammation in patients with relapsing-remitting multiple sclerosis. Eur J Nucl Med Mol Imaging. 2018;45:1423–31.CrossRefGoogle Scholar
  13. 13.
    Vomacka L, Albert NL, Lindner S, et al. TSPO imaging using the novel PET ligand [(18)F]GE-180: quantification approaches in patients with multiple sclerosis. EJNMMI Res. 2017;7:89.CrossRefGoogle Scholar
  14. 14.
    Dickstein LP, Zoghbi SS, Fujimura Y, et al. Comparison of F-18- and C-11-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography. Eur J Nucl Med Mol Imaging. 2011;38:352–7.CrossRefGoogle Scholar
  15. 15.
    Ikawa M, Lohith TG, Shrestha S, et al. 11C-ER176, a radioligand for 18-kDa translocator protein, has adequate sensitivity to robustly image all three affinity genotypes in human brain. J Nucl Med. 2017;58:320–5.CrossRefGoogle Scholar
  16. 16.
    Kreisl WC, Fujita M, Fujimura Y, et al. Comparison of [(11)C]-(R)-PK 11195 and [(11)C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: implications for positron emission tomographic imaging of this inflammation biomarker. NeuroImage. 2010;49:2924–32.CrossRefGoogle Scholar
  17. 17.
    Zanotti-Fregonara P, Zhang Y, Jenko KJ, et al. Synthesis and evaluation of translocator 18 kDa protein (TSPO) positron emission tomography (PET) radioligands with low binding sensitivity to human single nucleotide polymorphism rs6971. ACS Chem Neurosci. 2014;5:963–71.CrossRefGoogle Scholar
  18. 18.
    Owen DR, Gunn RN, Rabiner EA, et al. Mixed-affinity binding in humans with 18-kDa translocator protein ligands. J Nucl Med. 2011;52:24–32.CrossRefGoogle Scholar
  19. 19.
    Brown AK, Fujita M, Fujimura Y, et al. Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation. J Nucl Med. 2007;48:2072–9.CrossRefGoogle Scholar
  20. 20.
    Gauberti M, Montagne A, Quenault A, Vivien D. Molecular magnetic resonance imaging of brain-immune interactions. Front Cell Neurosci. 2014;8:389.CrossRefGoogle Scholar
  21. 21.
    Galldiks N, Ullrich R, Schroeter M, Fink GR, Jacobs AH, Kracht LW. Volumetry of [(11)C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme. Eur J Nucl Med Mol Imaging. 2010;37:84–92.CrossRefGoogle Scholar
  22. 22.
    Pirotte B, Goldman S, Massager N, et al. Comparison of 18F-FDG and 11C-methionine for PET-guided stereotactic brain biopsy of gliomas. J Nucl Med. 2004;45:1293–8.PubMedGoogle Scholar
  23. 23.
    van de Haar HJ, Burgmans S, Jansen JF, et al. Blood-brain barrier leakage in patients with early Alzheimer disease. Radiology. 2016;281:527–35.CrossRefGoogle Scholar
  24. 24.
    Montagne A, Zhao Z, Zlokovic BV. Alzheimer’s disease: a matter of blood-brain barrier dysfunction? J Exp Med. 2017;214:3151–69.CrossRefGoogle Scholar
  25. 25.
    van Assema DM, Lubberink M, Bauer M, et al. Blood-brain barrier P-glycoprotein function in Alzheimer’s disease. Brain. 2012;135:181–9.CrossRefGoogle Scholar
  26. 26.
    Deo AK, Borson S, Link JM, et al. Activity of P-glycoprotein, a beta-amyloid transporter at the blood-brain barrier, is compromised in patients with mild Alzheimer disease. J Nucl Med. 2014;55:1106–11.CrossRefGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Nantz National Alzheimer Center and Houston Methodist Research InstituteHoustonUSA
  2. 2.Department of Neuroimaging, Institute of Psychiatry, Psychology & NeuroscienceKings College LondonLondonUK
  3. 3.Department of NeurosurgeryHouston Methodist Hospital and Research InstituteHoustonUSA

Personalised recommendations