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动脉内注射卡铂和贝伐单抗在多形性胶质母细胞瘤C6大鼠胶质瘤模型中的疗效

Efficacy of intra-arterial carboplatin and bevacizumab in the C6 rat glioma model of glioblastoma multiforme.

作者信息

Lim Jaims, Santo Briana A, Baig Ammad A, Ciecierska Shiau-Sing K, Donnelly Brianna, Balghonaim Sarah, Levy Bennett R, Jaikumar Vinay, Levy Elad I, Tutino Vincent M, Siddiqui Adnan H

机构信息

Department of Neurosurgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA.

Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York, USA.

出版信息

J Neurointerv Surg. 2025 Jan 25. doi: 10.1136/jnis-2024-021789.

Abstract

BACKGROUND

Utilizing an endovascular rat glioma model, this study aimed to analyze the efficacy of intra-arterial (IA) carboplatin and bevacizumab delivery with blood-brain barrier breakdown (BBBB) for glioblastoma treatment.

METHODS

C6-glioma cells were stereotactically injected into the left frontal lobe of Wistar rats. Tumor growth was confirmed on day 8 via MRI. On day 9, a microcatheter was navigated under fluoroscopy from the left femoral artery to the left internal carotid artery. A volume of 2.25 mL of 25% mannitol was administered, followed by either 10 mg/kg of bevacizumab or 2.4 mg/kg of carboplatin. Serial MRI was obtained post-treatment to assess tumor response via analysis of tumor size and radiomics. Histology was analyzed after termination.

RESULTS

Control tumor rats and IA mannitol treated tumor rats had fatal tumor growths, with survival until 19.75±2.21 and 36.3±15.1 days, respectively. Carboplatin and bevacizumab treated rats lived >40 days, after which they were euthanized. From serial MRI and histology, IA carboplatin treated rats exhibited tumor regression and resolution by day 35. In IA bevacizumab treated rats, there was tumor regression near the basal ganglia of the brain, closer to the IA chemotherapy injection site, which had reorganized growth patterns. From MRI, 29 unique radiomic features were significantly different between control and treated tumors (notably for total energy and skewness), and treatment responders had a distinct, early manifesting radiomic profile.

CONCLUSION

IA carboplatin and bevacizumab treatment resulted in varying degrees of tumor suppression, validating the first endovascular C6 glioma model as a reliable method to assess new IA therapies.

摘要

背景

本研究利用血管内大鼠胶质瘤模型,旨在分析动脉内(IA)给予卡铂和贝伐单抗并破坏血脑屏障(BBBB)治疗胶质母细胞瘤的疗效。

方法

将C6胶质瘤细胞立体定向注射到Wistar大鼠的左额叶。在第8天通过MRI确认肿瘤生长。在第9天,在荧光透视引导下将微导管从左股动脉插入左颈内动脉。给予2.25 mL 25%的甘露醇,随后给予10 mg/kg的贝伐单抗或2.4 mg/kg的卡铂。治疗后进行系列MRI检查,通过分析肿瘤大小和放射组学来评估肿瘤反应。处死动物后进行组织学分析。

结果

对照肿瘤大鼠和IA甘露醇治疗的肿瘤大鼠出现致命的肿瘤生长,分别存活至19.75±2.21天和36.3±15.1天。卡铂和贝伐单抗治疗的大鼠存活超过40天,之后实施安乐死。从系列MRI和组织学检查来看,IA卡铂治疗的大鼠在第35天时肿瘤出现消退和溶解。在IA贝伐单抗治疗的大鼠中,靠近脑基底神经节、更靠近IA化疗注射部位的肿瘤出现消退,其生长模式发生了重组。从MRI检查结果来看,对照肿瘤和治疗后肿瘤之间有29个独特的放射组学特征存在显著差异(特别是总能量和偏度),且治疗反应者有独特的、早期表现的放射组学特征。

结论

IA卡铂和贝伐单抗治疗导致不同程度的肿瘤抑制,验证了首个血管内C6胶质瘤模型是评估新的IA治疗方法的可靠手段。

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