title: Antitumoral Effect of Sunitinib-eluting Beads in the Rabbit VX2 Tumor Model.
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.
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Pierre
authors.initials: P
authors.lastname: Bize
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Rafael
authors.initials: R
authors.lastname: Duran
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Katrin
authors.initials: K
authors.lastname: Fuchs
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Olivier
authors.initials: O
authors.lastname: Dormond
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Julien
authors.initials: J
authors.lastname: Namur
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Laurent A
authors.initials: LA
authors.lastname: Decosterd
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Olivier
authors.initials: O
authors.lastname: Jordan
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Eric
authors.initials: E
authors.lastname: Doelker
authors.affiliation: From the Departments of Radiology (P.B., R.D., A.D.), Surgery (O.D.), and Clinical Pharmacology (L.A.D.), University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland (K.F., O.J., E.D.); and Archimmed, Paris, France (J.N.).
authors.forename: Alban
authors.initials: A
authors.lastname: Denys
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D000077210:Sunitinib; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib