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18F-Fluoroethyl-tyrosine uptake is correlated with amino acid transport and neovascularization in treatment-naive glioblastomas

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Abstract

Purpose

To investigate the in vivo correlation between 18F-fluoroethyl-tyrosine (18F-FET) uptake and amino acid transporter expression and vascularization in treatment-naive glioblastomas.

Methods

A total of 43 stereotactic biopsies were obtained from 13 patients with suspected glioblastoma prior to therapy. All patients underwent a dynamic 18F-FET PET/MRI scan before biopsy. Immunohistochemistry was performed using antibodies against SLC7A5 (amino acid transporter), MIB-1 (Ki67, proliferation), CD31 (vascularization) and CA-IX (hypoxia). The intensity of staining was correlated with 18F-FET uptake and the dynamic 18F-FET uptake slope at the biopsy target point.

Results

In all patients, the final diagnosis was IDH-wildtype glioblastoma, WHO grade IV. Static 18F-FET uptake was significantly correlated with SLC7A5 staining (r = 0.494, p = 0.001). While the dynamic 18F-FET uptake slope did not show a significant correlation with amino acid transporter expression, it was significantly correlated with the number of CD31-positive vessels (r = −0.350, p = 0.031), which is line with earlier results linking 18F-FET kinetics with vascularization and perfusion. Besides, static 18F-FET uptake also showed correlations with CA-IX staining (r = 0.394, p = 0.009) and CD31 positivity (r = 0.410, p = 0.006). While the correlation between static 18F-FET uptake and SLC7A5 staining was confirmed as significant in multivariate analysis, this was not the case for the correlation with CD31 positivity, most likely because of the lower effect size and the relatively low number of samples. No significant correlation between 18F-FET uptake and Ki67 proliferation index was observed in our cohort.

Conclusion

Our results support the findings of preclinical studies suggesting that specific 18F-FET uptake in glioblastomas is mediated by amino acid transporters. As proposed previously, dynamic 18F-FET parameters might be more influenced by perfusion and therefore related to properties of the tumour neovascularization.

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Funding

This study was supported by funding from the German Research Foundation DFG (grants to C.P., S.F. and T.P.; FO 886/1-1, PR 1039/4-1).

Author information

Author notes

  1. Jens Gempt and Thomas Pyka contributed equally to this work.

Authors and Affiliations

  1. Department of Neuropathology, Institute of Pathology, Technische Universität München, Trogerstraße 18, 81675, Munich, Germany

    Friederike Liesche & Jürgen Schlegel

  2. Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany

    Mathias Lukas, Kuangyu Shi, Markus Schwaiger, Stefan Förster & Thomas Pyka

  3. Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Mathias Lukas

  4. Siemens Healthcare GmbH, Berlin, Germany

    Mathias Lukas

  5. Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany

    Christine Preibisch, Claus Zimmer & Thomas Pyka

  6. Department of Nuclear Medicine, Universität Bern, Hochschulstraße 6, 3012, Bern, Switzerland

    Kuangyu Shi

  7. Department of Neurosurgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany

    Bernhard Meyer & Jens Gempt

Authors
  1. Friederike Liesche
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  2. Mathias Lukas
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  3. Christine Preibisch
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  4. Kuangyu Shi
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  6. Bernhard Meyer
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  7. Markus Schwaiger
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  8. Claus Zimmer
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  9. Stefan Förster
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  10. Jens Gempt
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  11. Thomas Pyka
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Corresponding author

Correspondence to Thomas Pyka.

Ethics declarations

Conflicts of interest

B.M. and J.G. report personal fees from Brain Lab AG outside the submitted work. C.Z. has served on scientific advisory boards for Philips N.V. and Bayer Schering AG. All the other authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were approved by the Ethics Committee of the Medical Faculty of the Technische Universität München (vote 5547/12) and were in accordance with the principles of the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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This article is part of the Topical Collection on Oncology – Brain

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Liesche, F., Lukas, M., Preibisch, C. et al. 18F-Fluoroethyl-tyrosine uptake is correlated with amino acid transport and neovascularization in treatment-naive glioblastomas. Eur J Nucl Med Mol Imaging 46, 2163–2168 (2019). https://doi.org/10.1007/s00259-019-04407-3

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