The first endovascular rat glioma model for pre-clinical evaluation of intra-arterial therapeutics

Jaims Lim; Ammad A Baig; Brianna M Donnelly; Lee D Chaves; Suyog U Pol; Carmon Koenigsknecht; Donald Pionessa; Bennett R Levy; Liza Gutierrez; Vincent M Tutino; Elad I Levy; Adnan H Siddiqui

doi:10.1177/15910199231169597

The first endovascular rat glioma model for pre-clinical evaluation of intra-arterial therapeutics

Interv Neuroradiol. 2023 May 8:15910199231169597. doi: 10.1177/15910199231169597. Online ahead of print.

Authors

Jaims Lim^{1

2}, Ammad A Baig^{1

2}, Brianna M Donnelly^{1

2}, Lee D Chaves³, Suyog U Pol⁴, Carmon Koenigsknecht⁴, Donald Pionessa⁴, Bennett R Levy⁵, Liza Gutierrez⁴, Vincent M Tutino^{4

6

7}, Elad I Levy^{1

2

4

6}, Adnan H Siddiqui^{1

2

4

6}

Affiliations

¹ Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
² Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, NY, USA.
³ Department of Medicine, University of Kansas Medical Center, Kansas City, USA.
⁴ Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY, USA.
⁵ George Washington University School of Medicine, Washington, DC, USA.
⁶ Jacobs Institute, Buffalo, NY, USA.
⁷ Mechanical and Aerospace Engineering, University at Buffalo School of Engineering and Applied Sciences, Buffalo, NY, USA.

PMID: 37157800
DOI: 10.1177/15910199231169597

Abstract

Background: Several translational animal models have been described assessing intra-arterial (IA) treatments for malignant gliomas. We describe the first endovascular animal model that allows testing of IA drug delivery as a first-line treatment, which is difficult to do in actual patients. We report a unique protocol for vascular access and IA delivery in the rat model that, unlike prior reports, does not require direct puncture and opening of proximal cerebrovasculature which carries risk of ischemia in the animal brain post-delivery.

Methods: Wistar rats underwent left femoral artery catherization with a Balt Magic 1.2F catheter or Marathon Flow directed 1.5F Microcatheter with an Asahi Chikai 0.008 micro-guidewire which was navigated to the left internal carotid artery under x-ray. 25% mannitol was administered to test blood brain barrier breakdown (BBBB). Additional rats were implanted with C6 glioma cells in the left frontal lobe. C6 Glioma-Implanted Rats (C6GRs) were monitored for overall survival and tumor growth. Tumor volumes from MRI images were calculated utilizing 3D slicer. Additional rats underwent femoral artery catheterization with Bevacizumab, carboplatin, or irinotecan injected into the left internal carotid artery to test feasibility and safety.

Results: A successful endovascular access and BBBB protocol was established. BBBB was confirmed with positive Evans blue staining. 10 rats were successfully implanted with C6 gliomas with confirmed growths on MRI. Overall survival was 19.75 ± 2.21 days. 5 rats were utilized for the development of our femoral catheterization protocol and BBBB testing. With regards to IA chemotherapy dosage testing, control rats tolerated targeted 10 mg/kg of bevascizumab, 2.4 mg/kg of carboplatin, and 15 mg/kg of irinotecan IA ICA injections without any complications.

Conclusions: We present the first endovascular IA rat glioma model that allows selective catheterization of the intracranial vasculature and assessment of IA therapies for gliomas without need for access and sacrifice of proximal cerebrovasculature.

Keywords: GBM; Glioma; chemotherapy; endovascular; intra-arterial.