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

Details

Serval ID
serval:BIB_DBD572766E1D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antitumoral Effect of Sunitinib-eluting Beads in the Rabbit VX2 Tumor Model.
Journal
Radiology
Author(s)
Bize P., Duran R., Fuchs K., Dormond O., Namur J., Decosterd L.A., Jordan O., Doelker E., Denys A.
ISSN
1527-1315 (Electronic)
ISSN-L
0033-8419
Publication state
Published
Issued date
08/2016
Peer-reviewed
Oui
Volume
280
Number
2
Pages
425-435
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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
Animals, Antineoplastic Agents/administration & dosage, Antineoplastic Agents/therapeutic use, Disease Models, Animal, Indoles/administration & dosage, Indoles/therapeutic use, Liver Neoplasms, Experimental/drug therapy, Liver Neoplasms, Experimental/pathology, Pyrroles/administration & dosage, Pyrroles/therapeutic use, Rabbits, Tumor Burden, Vascular Endothelial Growth Factor A/drug effects
Pubmed
Open Access
Yes
Create date
27/02/2016 15:08
Last modification date
20/08/2019 17:00
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