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Title

Antitumoral Effect of Sunitinib-eluting Beads in the Rabbit VX2 Tumor Model

Authors
Bize, Pierre
Duran, Rafael
Dormond, Olivier
Namur, Julien
Decosterd, Laurent A
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Published in Radiology. 2016, vol. 280, no. 2, p. 425-435
Abstract Purpose To measure plasmatic sunitinib concentration (PSC) and intratumoral sunitinib concentration (ITSC) after transcatheter arterial chemoembolization (TACE) with two different sizes of sunitinib-eluting beads (SEBs) in rabbits with VX2 hepatic allografts and to investigate treatment effects on vascular endothelial growth factor receptor type 2 (VEGFR2) phosphorylation, tumor volume, and histopathologic changes. Materials and Methods The protocol was approved by the French Ethics Committee for Animal Experiments (Comité d'Ethique en Expérimentation Animale du Centre INRA de Jouy-en-Josas et AgroParisTech, or COMETHEA, approval no. 11/028). Two experiments were performed. In the first, seven animals received 0.05 mL of 100-300-μm SEBs (1.5 mg of sunitinib) in the hepatic artery, and six animals received saline injections. In the second, eight animals received 0.05 mL of 70-150-μm SEBs (1.5 mg of sunitinib), seven received 0.05 mL of 70-150-μm unloaded beads, and seven received oral sunitinib (6 mg every day). Tumor size was monitored with ultrasonography. PSC, ITSC, and phosphorylation of VEGFR2 were assessed on days 1 and 14. After the animals were sacrificed, histopathologic analysis was performed. The Kruskal-Wallis test, Mann-Whitney U test, and Fisher exact test were used to look for statistically significant differences between groups. Results Maximum PSC after TACE with 100-300-μm SEBs was 0.002 μg/mL on day 1. ITSC was 17.8 μg/g on day 1 and 0.16 μg/g on day 14. After TACE with 70-150-μm SEBs, ITSC was 40.4 μg/g on day 1 and 27.4 μg/g on day 14. Phosphorylation of VEGFR2 was inhibited until day 14 after TACE with both sizes of SEBs. The size of VX2 tumors treated with 70-150-μm SEB TACE increased less (-2%) than that of tumors treated with unloaded beads (+42%) and oral sunitinib (6 mg every day; +1853%; P = .044). Conclusion SEB TACE resulted in minimal PSC, high ITSC, and sustained VEGFR2 phosphorylation inhibition until day 14. (©) RSNA, 2016.
Keywords AnimalsAntineoplastic Agents/administration & dosage/therapeutic useDisease Models, AnimalIndoles/administration & dosage/therapeutic useLiver Neoplasms, Experimental/drug therapy/pathologyPyrroles/administration & dosage/therapeutic useRabbitsSunitinibTumor BurdenVascular Endothelial Growth Factor A/drug effects
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PMID: 26919561
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Research group Biopharmacie
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BIZE, Pierre et al. Antitumoral Effect of Sunitinib-eluting Beads in the Rabbit VX2 Tumor Model. In: Radiology, 2016, vol. 280, n° 2, p. 425-435. doi: 10.1148/radiol.2016150361 https://archive-ouverte.unige.ch/unige:141546

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Deposited on : 2020-09-18

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