nach oben

European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

19.08.2017 | Original Article

TSPO PET for glioma imaging using the novel ligand ¹⁸F-GE-180: first results in patients with glioblastoma

verfasst von: Nathalie L. Albert, M. Unterrainer, D. F. Fleischmann, S. Lindner, F. Vettermann, A. Brunegraf, L. Vomacka, M. Brendel, V. Wenter, C. Wetzel, R. Rupprecht, J.-C. Tonn, C. Belka, P. Bartenstein, M. Niyazi

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 13/2017

Einloggen, um Zugang zu erhalten

Abstract

Objective

The 18-kDa mitochondrial translocator protein (TSPO) was reported to be upregulated in gliomas. ¹⁸F-GE-180 is a novel 3rd generation TSPO receptor ligand with improved target-to-background contrast compared to previous tracers. In this pilot study, we compared PET imaging with ¹⁸F-GE-180 and MRI of patients with untreated and recurrent pretreated glioblastoma.

Methods

Eleven patients with histologically confirmed IDH wildtype gliomas (10 glioblastomas, 1 anaplastic astrocytoma) underwent ¹⁸F-GE-180 PET at initial diagnosis or recurrence. The PET parameters mean background uptake (SUV_BG), maximal tumour-to-background ratio (TBR_max) and PET volume using different thresholds (SUV_BG × 1.6, 1.8 and 2.0) were evaluated in the 60-80 min p.i. summation images. The different PET volumes were compared to the contrast-enhancing tumour volume on MRI.

Results

All gliomas were positive on ¹⁸F-GE-180 PET and were depicted with extraordinarily high tumour-to-background contrast (median SUV_BG 0.47 (0.37-0.93), TBR_max 6.61 (3.88-9.07)). ¹⁸F-GE-180 uptake could be found even in areas without contrast enhancement on MRI, leading to significantly larger PET volumes than MRI-based volumes (median 90.5, 74.5, and 63.8 mL vs. 31.0 mL; p = 0.003, 0.004, 0.013). In percentage difference, the PET volumes were on average 179%, 135%, and 90% larger than the respective MRI volumes. The median spatial volumetric correlation (Sørensen-Dice coefficient) of PET volumes and MRI volumes prior to radiotherapy was 0.48, 0.54, and 0.58.

Conclusion

¹⁸F-GE-180 PET provides a remarkably high tumour-to-background contrast in untreated and pretreated glioblastoma and shows tracer uptake even beyond contrast enhancement on MRI. To what extent ¹⁸F-GE-180 uptake reflects the tumour extent of human gliomas and inflammatory cells remains to be evaluated in future prospective studies with guided stereotactic biopsies and correlation of histopathological results.

Nur mit Berechtigung zugänglich

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–66. doi:10.1016/S1470-2045(09)70025-7.CrossRefPubMed

Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1100–8. doi:10.1016/S1470-2045(14)70379-1.CrossRefPubMed

Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370:699–708. doi:10.1056/NEJMoa1308573.CrossRefPubMedPubMedCentral

Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014;15:e395–403. doi:10.1016/S1470-2045(14)70011-7.CrossRefPubMed

Suchorska B, Albert NL, Tonn JC. Usefulness of PET imaging to guide treatment options in gliomas. Curr Treat Options Neurol. 2016;18:4. doi:10.1007/s11940-015-0384-z.CrossRefPubMed

Hutterer M, Hattingen E, Palm C, Proescholdt MA, Hau P. Current standards and new concepts in MRI and PET response assessment of antiangiogenic therapies in high-grade glioma patients. Neuro-Oncology. 2015;17:784–800. doi:10.1093/neuonc/nou322.CrossRefPubMed

Galldiks N, Langen KJ, Pope WB. From the clinician’s point of view - what is the status quo of positron emission tomography in patients with brain tumors? Neuro-Oncology. 2015; doi:10.1093/neuonc/nov118.

Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM, et al. Response assessment in neuro-oncology working group and European Association for neuro-oncology recommendations for the clinical use of PET imaging in gliomas. Neuro-Oncology. 2016;18:1199–208. doi:10.1093/neuonc/now058.CrossRefPubMedPubMedCentral

Owen DR, Matthews PM. Imaging brain microglial activation using positron emission tomography and translocator protein-specific radioligands. Int Rev Neurobiol. 2011;101:19–39. doi:10.1016/B978-0-12-387718-5.00002-X.CrossRefPubMed

10.

Batarseh A, Papadopoulos V. Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Mol Cell Endocrinol. 2010;327:1–12. doi:10.1016/j.mce.2010.06.013.CrossRefPubMedPubMedCentral

11.

Batarseh A, Li J, Papadopoulos V. Protein kinase C epsilon regulation of translocator protein (18 kDa) Tspo gene expression is mediated through a MAPK pathway targeting STAT3 and c-Jun transcription factors. Biochemistry. 2010;49:4766–78. doi:10.1021/bi100020e.CrossRefPubMedPubMedCentral

12.

Katz Y, Ben-Baruch G, Kloog Y, Menczer J, Gavish M. Increased density of peripheral benzodiazepine-binding sites in ovarian carcinomas as compared with benign ovarian tumours and normal ovaries. Clin Sci (Lond). 1990;78:155–8.CrossRef

13.

Katz Y, Eitan A, Gavish M. Increase in peripheral benzodiazepine binding sites in colonic adenocarcinoma. Oncology. 1990;47:139–42.CrossRefPubMed

14.

Vlodavsky E, Soustiel JF. Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival. J Neuro-Oncol. 2007;81:1–7. doi:10.1007/s11060-006-9199-9.CrossRef

15.

Roncaroli F, Su Z, Herholz K, Gerhard A, Turkheimer FE. TSPO expression in brain tumours: is TSPO a target for brain tumour imaging? Clin Transl imaging. 2016;4:145–56. doi:10.1007/s40336-016-0168-9.CrossRefPubMedPubMedCentral

16.

Awde AR, Boisgard R, Theze B, Dubois A, Zheng J, Dolle F, et al. The translocator protein radioligand 18F-DPA-714 monitors antitumor effect of erufosine in a rat 9L intracranial glioma model. J Nucl Med Off Publ Soc Nucl Med. 2013;54:2125–31. doi:10.2967/jnumed.112.118794.

17.

Buck JR, McKinley ET, Fu A, Abel TW, Thompson RC, Chambless L, et al. Preclinical TSPO ligand PET to visualize human glioma xenotransplants: a preliminary study. PLoS One. 2015;10:e0141659. doi:10.1371/journal.pone.0141659.CrossRefPubMedPubMedCentral

18.

Tang D, Hight MR, McKinley ET, Fu A, Buck JR, Smith RA, et al. Quantitative preclinical imaging of TSPO expression in glioma using N,N-diethyl-2-(2-(4-(2-18F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimi din-3-yl)acetamide. J Nucl Med Off Publ Soc Nucl Med. 2012;53:287–94. doi:10.2967/jnumed.111.095653.

19.

Winkeler A, Boisgard R, Awde AR, Dubois A, Theze B, Zheng J, et al. The translocator protein ligand [(1)(8)F]DPA-714 images glioma and activated microglia in vivo. Eur J Nucl Med Mol Imaging. 2012;39:811–23. doi:10.1007/s00259-011-2041-4.CrossRefPubMedPubMedCentral

20.

Tang D, Nickels ML, Tantawy MN, Buck JR, Manning HC. Preclinical imaging evaluation of novel TSPO-PET ligand 2-(5,7-diethyl-2-(4-(2-[(18)F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)- N,N-diethylacetamide ([ (18)F]VUIIS1008) in glioma. Mol Imaging Biol MIB Off Publ Acad Mol Imaging. 2014;16:813–20. doi:10.1007/s11307-014-0743-2.CrossRef

21.

Su Z, Roncaroli F, Durrenberger PF, Coope DJ, Karabatsou K, Hinz R, et al. The 18-kDa mitochondrial translocator protein in human gliomas: an 11C-(R)PK11195 PET imaging and neuropathology study. J Nucl Med Off Publ Soc Nucl Med. 2015;56:512–7. doi:10.2967/jnumed.114.151621.

22.

Takaya S, Hashikawa K, Turkheimer FE, Mottram N, Deprez M, Ishizu K, et al. The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas. J Neuro-Oncol. 2007;85:95–103. doi:10.1007/s11060-007-9396-1.CrossRef

23.

Junck L, Olson JM, Ciliax BJ, Koeppe RA, Watkins GL, Jewett DM, et al. PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site. Ann Neurol. 1989;26:752–8. doi:10.1002/ana.410260611.CrossRefPubMed

24.

Pappata S, Cornu P, Samson Y, Prenant C, Benavides J, Scatton B, et al. PET study of carbon-11-PK 11195 binding to peripheral type benzodiazepine sites in glioblastoma: a case report. J Nucl Med Off Publ Soc Nucl Med. 1991;32:1608–10.

25.

Owen DR, Howell OW, Tang SP, Wells LA, Bennacef I, Bergstrom M, et al. Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2010;30:1608–18. doi:10.1038/jcbfm.2010.63.CrossRef

26.

Wadsworth H, Jones PA, Chau WF, Durrant C, Fouladi N, Passmore J, 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. doi:10.1016/j.bmcl.2011.12.084.CrossRefPubMed

27.

Boutin H, Murray K, Pradillo J, Maroy R, Smigova A, Gerhard A, 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. doi:10.1007/s00259-014-2939-8.CrossRefPubMed

28.

Dickens AM, Vainio S, Marjamaki P, Johansson J, Lehtiniemi P, Rokka J, et al. Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180. J Nucl Med Off Publ Soc Nucl Med. 2014;55:466–72. doi:10.2967/jnumed.113.125625.

29.

Fan Z, Calsolaro V, Atkinson RA, Femminella GD, Waldman A, Buckley C, et al. Flutriciclamide (18F-GE180) PET: first in human PET study of novel 3rd generation in vivo marker of human translator protein. J Nucl Med Off Publ Soc Nucl Med. 2016; doi:10.2967/jnumed.115.169078.

30.

Feeney C, Scott G, Raffel J, Roberts S, Coello C, Jolly A, 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. doi:10.1007/s00259-016-3444-z.CrossRefPubMedPubMedCentral

31.

Brendel M, Probst F, Jaworska A, Overhoff F, Korzhova V, Albert NL, et al. Glial activation and glucose metabolism in a transgenic Amyloid mouse model: a triple-tracer PET study. J Nucl Med Off Publ Soc Nucl Med. 2016;57:954–60. doi:10.2967/jnumed.115.167858.

32.

Vomacka LA, Albert N, Lindner S, Unterrainer M, Mahler C, Brendel M, et al. Quantification of the new TSPO ligand [18F]GE-180 in patients with multiple sclerosis - initial results. J Nucl Med Off Publ Soc Nucl Med. 2017;58:208.

33.

Jansen NL, Suchorska B, Wenter V, Schmid-Tannwald C, Todica A, Eigenbrod S, et al. Prognostic significance of dynamic 18F-FET PET in newly diagnosed astrocytic high-grade glioma. J Nucl Med Off Publ Soc Nucl Med. 2015;56:9–15. doi:10.2967/jnumed.114.144675.

34.

Albert NL, Winkelmann I, Suchorska B, Wenter V, Schmid-Tannwald C, Mille E, et al. Early static (18)F-FET-PET scans have a higher accuracy for glioma grading than the standard 20-40 min scans. Eur J Nucl Med Mol Imaging. 2016;43:1105–14. doi:10.1007/s00259-015-3276-2.CrossRefPubMed

35.

Romagna A, Unterrainer M, Schmid-Tannwald C, Brendel M, Tonn JC, Nachbichler SB, et al. Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18F]FET- PET overcome diagnostic uncertainties? Radiat Oncol (Lond Engl). 2016;11:139. doi:10.1186/s13014-016-0713-8.CrossRef

36.

Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Muller HW, et al. O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128:678–87. doi:10.1093/brain/awh399.CrossRefPubMed

37.

Mehrkens JH, Popperl G, Rachinger W, Herms J, Seelos K, Tatsch K, et al. The positive predictive value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET in the diagnosis of a glioma recurrence after multimodal treatment. J Neuro-Oncol. 2008;88:27–35. doi:10.1007/s11060-008-9526-4.CrossRef

38.

Niyazi M, Brada M, Chalmers AJ, Combs SE, Erridge SC, Fiorentino A, et al. ESTRO-ACROP guideline “target delineation of glioblastomas”. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2016;118:35–42. doi:10.1016/j.radonc.2015.12.003.CrossRef

39.

Buck JR, McKinley ET, Hight MR, Fu A, Tang D, Smith RA, et al. Quantitative, preclinical PET of translocator protein expression in glioma using 18F-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline. J Nucl Med Off Publ Soc Nucl Med. 2011;52:107–14. doi:10.2967/jnumed.110.081703.

40.

Su Z, Herholz K, Gerhard A, Roncaroli F, Du Plessis D, Jackson A, et al. [(1)(1)C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur J Nucl Med Mol Imaging. 2013;40:1406–19. doi:10.1007/s00259-013-2447-2.CrossRefPubMedPubMedCentral

41.

Tarkkonen A, Rissanen E, Tuokkola T, Airas L. Utilization of PET imaging in differential diagnostics between a tumefactive multiple sclerosis lesion and low-grade glioma. Mult Scler Relat Disord. 2016;9:147–9. doi:10.1016/j.msard.2016.07.016.CrossRefPubMed

42.

Rapp M, Heinzel A, Galldiks N, Stoffels G, Felsberg J, Ewelt C, et al. Diagnostic performance of 18F-FET PET in newly diagnosed cerebral lesions suggestive of glioma. J Nucl Med Off Publ Soc Nucl Med. 2013;54:229–35. doi:10.2967/jnumed.112.109603.

43.

Hutterer M, Nowosielski M, Putzer D, Jansen NL, Seiz M, Schocke M, et al. [18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma. Neuro-Oncology. 2013;15:341–51. doi:10.1093/neuonc/nos300.CrossRefPubMedPubMedCentral

44.

Popperl G, Gotz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K. Value of O-(2-[18F]fluoroethyl)- L-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging. 2004;31:1464–70. doi:10.1007/s00259-004-1590-1.CrossRefPubMed

45.

Nikaki A, Angelidis G, Efthimiadou R, Tsougos I, Valotassiou V, Fountas K, et al. 18F-fluorothymidine PET imaging in gliomas: an update. Ann Nucl Med. 2017; doi:10.1007/s12149-017-1183-2.

46.

Jensen P, Feng L, Law I, Svarer C, Knudsen GM, Mikkelsen JD, et al. TSPO imaging in glioblastoma multiforme: a direct comparison between 123I-CLINDE SPECT, 18F-FET PET, and gadolinium-enhanced MR imaging. J Nucl Med Off Publ Soc Nucl Med. 2015;56:1386–90. doi:10.2967/jnumed.115.158998.

47.

Badie B, Schartner JM. Flow cytometric characterization of tumor-associated macrophages in experimental gliomas. Neurosurgery. 2000;46:957–62.PubMed

Titel: TSPO PET for glioma imaging using the novel ligand 18F-GE-180: first results in patients with glioblastoma
verfasst von: Nathalie L. Albert
M. Unterrainer
D. F. Fleischmann
S. Lindner
F. Vettermann
A. Brunegraf
L. Vomacka
M. Brendel
V. Wenter
C. Wetzel
R. Rupprecht
J.-C. Tonn
C. Belka
P. Bartenstein
M. Niyazi
Publikationsdatum: 19.08.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 13/2017
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-017-3799-9

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 13/2017

18F-FDG PET/CT of extensive rheumatoid nodulosis

Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET

Individualized risk assessment in neuroblastoma: does the tumoral metabolic activity on 123I-MIBG SPECT predict the outcome?

Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

Prognostic value of atherosclerotic burden and coronary vascular function in patients with suspected coronary artery disease

Validation and head-to-head comparison of three nomograms predicting probability of lymph node invasion of prostate cancer in patients undergoing extended and/or sentinel lymph node dissection