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Fluorescence imaging of meningioma cells with somatostatin receptor ligands: an in vitro study

  • Original Article - Tumor - Meningioma
  • Published:
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Abstract

Background

The use of five-aminolevulinic acid (5-ALA) in the staining of malignant glioma cells has significantly improved intraoperative radicality in the resection of gliomas in the last decade. Currently, there is no comparable selective fluorescent substance available for meningiomas. There is however a demand for intraoperative fluorescent identification of, e.g., invasive skull base meningiomas to help improve safe radical resection. Meningiomas show high expression of the somatostatin receptor type 2, offering the possibility of receptor-targeted imaging. The authors used a somatostatin receptor-labeled fluorescence dye in the identification of meningiomas in vitro. The aim of this study was to evaluate the possibility of selective identification of meningioma cells with fluorescent techniques.

Methods

Twenty-four primary human meningioma cell cultures were analyzed. The tumor cells were incubated with FAM-TOC (5,6-Carboxyfluoresceine-Tyr3-Octreotide). As a negative control, four human dura tissues were cultured as well as a mixed cell culture in vitro and incubated with the same somatostatin receptor-labeled fluorescence substance. After incubation, fluorescence signal and intensity in all cell cultures were analyzed at three different time points using a fluorescence microscope with 488 nm epi-illumination.

Results

Sixteen WHO I, six WHO II, two WHO III meningioma primary cell cultures, and four dura cell cultures were analyzed. Fluorescence was detected in all meningioma cell cultures (22 cell culture stained strongly, 2 cell cultures moderately) directly after incubation up until 4 h later. There were no differences in the quality and quantity of fluorescence signal between the various meningioma grades. The fluorescence signal persisted unchanged during the analyzed period. In the negative control, dura cell cultures remained unstained.

Conclusions

This study demonstrates the use of FAM-TOC in the selective fluorescent identification of meningioma cells in vitro. Further evaluation of the chemical kinetics of the applied somatostatin receptor ligand and fluorescence dye is warranted. As a next step, an experimental animal model is needed to evaluate these promising results in vivo.

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Abbreviations

5-ALA:

Five-aminolevulinic acid

CO2 :

Carbon dioxide

DAPI:

4′,6-diamidin-2-phenylindol

DMEM:

Dulbecco’s modified Eagle medium

FAM-TOC:

6-Carboxyfluorescein-Tyrosin3-Octreotide

FCS:

Fetal calf serum

HE:

Hematoxylin and eosin

Na-Fl:

Sodium fluorescein

PBS:

Phosphate-buffered saline

PFA:

Paraformaldehyde

ROI:

Region of interest

SPECT:

Single-photon emission computed tomography

SSTR:

Somatostatin receptor

WHO:

World Health Organization

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Acknowledgements

The authors thank Mrs. Sigrid Welsch for technical assistance during cell culture and fluorescence labeling of the cell cultures, and Mr. David Breuskin and Mr. Sam Orie for proofreading of the manuscript.

Funding

The Saarland University provided financial support in the form of the grant HOMFOR 2016-201000790. The sponsor had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes, 66421, Homburg, Saar, Germany

    Stefan Linsler, Ralf Ketter, Joachim Oertel & Steffi Urbschat

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  1. Stefan Linsler
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  2. Ralf Ketter
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  3. Joachim Oertel
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  4. Steffi Urbschat
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Correspondence to Stefan Linsler.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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

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Comments

Very interesting if this flourescence could be of clinical use in the future. These results are very early but if proven specific enough with respect to per example invasion of dura there is a big potential.

Jane Skjoth-Rasmussen

Copenhagen, Denmark

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This article is part of the Topical Collection on Tumor - Meningioma

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Linsler, S., Ketter, R., Oertel, J. et al. Fluorescence imaging of meningioma cells with somatostatin receptor ligands: an in vitro study. Acta Neurochir 161, 1017–1024 (2019). https://doi.org/10.1007/s00701-019-03872-x

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  • DOI: https://doi.org/10.1007/s00701-019-03872-x

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