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

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.