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Basic science
Original research
Efficacy of intra-arterial carboplatin and bevacizumab in the C6 rat glioma model of glioblastoma multiforme
  1. Jaims Lim1,2,3,
  2. Briana A Santo2,4,
  3. Ammad A Baig1,
  4. Shiau-Sing K Ciecierska5,
  5. Brianna Donnelly6,
  6. Sarah Balghonaim4,
  7. Bennett R Levy7,
  8. Vinay Jaikumar1,
  9. Elad I Levy1,3,8,
  10. Vincent M Tutino1,4,
  11. Adnan H Siddiqui1,3,8
    1. 1Department of Neurosurgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA
    2. 2Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York, USA
    3. 3Department of Neurosurgery, Gates Vascular Institute, Buffalo, New York, USA
    4. 4Department of Pathology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA
    5. 5University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA
    6. 6Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
    7. 7Department of Neurosurgery, New York University, New York, New York, USA
    8. 8Department of Radiology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA
    1. Correspondence to Dr Adnan H Siddiqui; asiddiqui{at}ubns.com

    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.

    • Technique
    • Tumor
    • Brain
    • Drug
    • MRI

    Data availability statement

    Data are available upon reasonable request. All study data are described in the manuscript.

    https://doi.org/10.1136/jnis-2024-021789

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      Data availability statement

      Data are available upon reasonable request. All study data are described in the manuscript.

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      Footnotes

      • X @amdbaig, @bdonnelly718

      • Contributors All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by JL, BAS, AAB, S-SC, BMD, BRL, VJ, and VMT. The first draft of the manuscript was written by JL, BAS and VMT and all authors commented on previous versions of the manuscript. JL, BAS, SB, and VMT contributed to revision of the manuscript. All authors read and approved the final manuscript.

      • Funding This study was funded, in part, by the Society of Vascular and Interventional Neurology Pilot Research Grant (JL) and the Thomas F. Frawley MD Research Fellowship Award (JL).

      • Competing interests JL: Research Support: The Society of Vascular and Interventional Neurology Pilot Research Grant, and the Thomas F. Frawley MD Research Fellowship Award. BAS: None. AAB: None. S-SKC: None. BD: None. SB: None. BRL: None. VJ: None. EIL: Board Membership: Stryker, NeXtGen Biologics, MedX Health, Cognition Medical, EndoStream; Consultancy: Claret Medical, GLG Consulting, Guidepoint, Imperative Care, Medtronic, Rebound Therapeutics, StimMed; Employment: University at Buffalo Neurosurgery Inc; Expert Testimony: renders medical/legal opinions as an expert witness; Stock/Stock Options: NeXtGen Biologics, Cognition Medical, Rapid Medical, Claret Medical, Imperative Care, Rebound Therapeutics, StimMed. VMT: Financial Interest/Investor/Stock Options/Ownership: Neurovascular Diagnostics, Inc, QAS.ai, Inc. Grant Support: Brain Aneurysm Foundation, National Science Foundation Award No. 1746694, NIH NINDS award R43 NS115314-0, clinical and translational science institute grant from the national Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001412 to the University at Buffalo. Consultant/Advisory Board: Canon Medical Systems America. AHS: Financial Interest/Investor/Stock Options/Ownership: Adona Medical, Inc, Amnis Therapeutics, Bend IT Technologies, Ltd, BlinkTBI, Inc, Buffalo Technology Partners, Inc, Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc, Cerevatech Medical, Inc, Cognition Medical, CVAID Ltd, Endostream Medical, Ltd, Imperative Care, Inc, Instylla, Inc, International Medical Distribution Partners, Launch NY, Inc, NeuroRadial Technologies, Inc, Neurotechnology Investors, Neurovascular Diagnostics, Inc, PerFlow Medical, Ltd, Q’Apel Medical, Inc, QAS.ai, Inc, Radical Catheter Technologies, Inc, Rebound Therapeutics Corp (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc (purchased 2020 by Medtronic), Sense Diagnostics, Inc, Serenity Medical, Inc, Silk Road Medical, SongBird Therapy, Spinnaker Medical, Inc, StimMed, LLC, Synchron, Inc, Three Rivers Medical, Inc, Truvic Medical, Inc, Tulavi Therapeutics, Inc, Vastrax, LLC, VICIS, Inc, Viseon, Inc. Consultant/Advisory Board: National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001412 to the University at Buffalo.

      • Provenance and peer review Not commissioned; externally peer reviewed.

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