Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes, 66421, Homburg, Saar, Germany.
Acta Neurochir (Wien). 2019 May;161(5):1017-1024. doi: 10.1007/s00701-019-03872-x. Epub 2019 Mar 15.
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.
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.
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.
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.
在过去十年中，使用 5-氨基酮戊酸（5-ALA）对恶性神经胶质瘤细胞进行染色，显著提高了神经胶质瘤切除术的术中根治性。目前，尚无可用于脑膜瘤的可比选择性荧光物质。然而，人们需要在术中对侵袭性颅底脑膜瘤等进行荧光识别，以帮助提高安全根治性切除。脑膜瘤表现出高表达生长抑素受体 2，这为受体靶向成像提供了可能性。作者使用生长抑素受体标记的荧光染料来鉴定体外脑膜瘤。本研究旨在评估使用荧光技术选择性鉴定脑膜瘤细胞的可能性。
分析了 24 例原发性人脑膜瘤细胞培养物。将肿瘤细胞与 FAM-TOC（5,6-羧基荧光素-Tyr3-奥曲肽）孵育。作为阴性对照，培养了 4 个人脑膜组织以及体外混合细胞培养物，并与相同的生长抑素受体标记的荧光物质孵育。孵育后，在荧光显微镜下使用 488nm epi 照明在三个不同时间点分析所有细胞培养物的荧光信号和强度。
分析了 16 例 WHO I 级、6 例 WHO II 级、2 例 WHO III 级脑膜瘤原代细胞培养物和 4 例脑膜细胞培养物。孵育后直接检测到所有脑膜瘤细胞培养物（22 个细胞培养物强烈染色，2 个细胞培养物中度染色），直到 4 小时后。不同脑膜瘤分级之间的荧光信号质量和数量没有差异。在分析期间，荧光信号保持不变。在阴性对照中，脑膜细胞培养物保持未染色。
本研究证明了 FAM-TOC 在体外选择性荧光鉴定脑膜瘤细胞中的应用。需要进一步评估所应用的生长抑素受体配体和荧光染料的化学动力学。作为下一步，需要实验动物模型来体内评估这些有前途的结果。
