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

Abstract

BackgroundUtilizing 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.MethodsC6-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.ResultsControl 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.ConclusionIA 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.