Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model
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LABORATORY INVESTIGATION
INTERVENTIONAL ONCOLOGY
Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model Andrew C. Gordon1,2 • Sarah B. White3 • Yihe Yang1 • Vanessa L. Gates1 Daniel Procissi1 • Kathleen R. Harris1 • Zhuoli Zhang1 • Tianchu Lyu1 • Xiaoke Huang1 • Matthew R. Dreher4 • Reed A. Omary5 • Riad Salem1,6,7 • Robert J. Lewandowski1,6,7 • Andrew C. Larson1,2
•
Received: 17 March 2020 / Accepted: 25 May 2020 Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2020
Abstract Purpose To evaluate the combination of 90Y radioembolization (Y90) and drug-eluting bead irinotecan (DEBIRI) microspheres in the VX2 rabbit model. Materials and Methods An initial dose finding study was performed in 6 White New Zealand rabbits to identify a therapeutic but subcurative dose of Y90. In total, 29 rabbits were used in four groups: Y90 treatment (n = 8), DEBIRI treatment (n = 6), Y90 ? DEBIRI treatment (n = 7), and an untreated control group (n = 8). Hepatic toxicity was Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00270-020-02538-x) contains supplementary material, which is available to authorized users. & Andrew C. Gordon [email protected] Andrew C. Larson [email protected] 1
Department of Radiology, Northwestern University Feinberg School of Medicine, 737 N. Michigan Ave, 16th Floor, Chicago, IL 60611, USA
2
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA
3
Department of Radiology, Division of Vascular and Interventional Radiology, Medical College of Wisconsin, Milwaukee, WI, USA
4
BTG International Inc, West Conshohocken, PA, USA
5
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
6
Department of Medicine-Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
7
Department of Surgery-Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
evaluated at baseline, 24 h, 72 h, 1 week, and 2 weeks. MRI tumor volume (TV) and enhancing tumor volume were assessed baseline and 2 weeks. Tumor area and necrosis were evaluated on H&E for pathology. Results Infused activities of 84.0–94.4 MBq (corresponding to 55.1–72.7 Gy) were selected based on the initial dose finding study. Infusion of DEBIRI after Y90 was technically feasible in all cases (7/7). Overall, 21/29 animals survived to 2 weeks, and the remaining animals had extrahepatic disease on necropsy. Liver transaminases were elevated with Y90, DEBIRI, and Y90 ? DEBIRI compared to control at 24 h, 72 h, and 1 week post-treatment and returned to baseline by 2 weeks. By TV, Y90 ? DEBIRI was the only treatment to show statistically significant reduction at 2 weeks compared to the control group (p = 0.012). The change in tumor volume (week 2— baseline) for both Y90 ? DEBIRI versus control (p = 0.00
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