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基于近红外荧光标记的适体实现脑肿瘤可视化,用于荧光引导手术。

Visualization of Brain Tumors with Infrared-Labeled Aptamers for Fluorescence-Guided Surgery.

机构信息

Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk 660022, Russia.

Aptamerlab LLC, Krasnoyarsk 660042, Russia.

出版信息

J Am Chem Soc. 2024 Sep 11;146(36):24989-25004. doi: 10.1021/jacs.4c06716. Epub 2024 Aug 26.

Abstract

Gliomas remain challenging brain tumors to treat due to their infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful resection. This study introduces an innovative intraoperative visualization method utilizing surgical fluorescence microscopy to precisely locate tumor cell dissemination. Here, the focus is on the development of a novel contrasting agent (IR-Glint) for intraoperative visualization of human glial tumors comprising infrared-labeled Glint aptamers. The specificity of IR-Glint is assessed using flow cytometry and microscopy on primary cell cultures. In vivo effectiveness is studied on mouse and rabbit models, employing orthotopic xenotransplantation of human brain gliomas with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. The experiments validate the potential of IR-Glint for the intraoperative visualization of gliomas using infrared imaging. IR-Glint penetrates the blood-brain barrier and can be used for both intravenous and surface applications, allowing clear visualization of the tumor. The surface application directly to the brain reduces the dosage required and mitigates potential toxic effects on the patient. The research shows the potential of infrared dye-labeled aptamers for accurately visualizing glial tumors during brain surgery. This novel aptamer-assisted fluorescence-guided surgery (AptaFGS) may pave the way for future advancements in the field of neurosurgery.

摘要

由于其浸润性的性质,神经胶质瘤仍然是治疗具有挑战性的脑肿瘤。在手术中准确识别肿瘤边界对于成功切除至关重要。本研究介绍了一种利用手术荧光显微镜精确定位肿瘤细胞扩散的创新术中可视化方法。这里的重点是开发一种新型对比剂(IR-Glint),用于包含红外标记的 Glint 适体的人类神经胶质瘤的术中可视化。使用流式细胞术和显微镜评估了针对原代细胞培养物的 IR-Glint 的特异性。在小鼠和兔模型中研究了体内效果,使用各种成像技术,包括 PET/CT、体内荧光可视化、共聚焦激光扫描和手术显微镜,进行了人脑神经胶质瘤的原位异种移植。实验验证了使用红外成像进行神经胶质瘤术中可视化的 IR-Glint 的潜力。IR-Glint 穿透血脑屏障,可用于静脉内和表面应用,可清晰地可视化肿瘤。直接将其应用于大脑表面可以减少所需的剂量,并减轻对患者的潜在毒性影响。研究表明,红外染料标记适体在脑外科手术中准确可视化神经胶质瘤的潜力。这种新型适体辅助荧光引导手术(AptaFGS)可能为神经外科学领域的未来发展铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86ca/11404482/d9e3bbd00aaa/ja4c06716_0001.jpg

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