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Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect

Authors
 Gyoung Min Kim  ;  Man Deuk Kim  ;  Do Young Kim  ;  Se Hoon Kim  ;  Jong Yun Won  ;  Sung Il Park  ;  Do Yun Lee  ;  Wonseon Shin  ;  Minwoo Shin 
Citation
 JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY, Vol.27(7) : 1086-1092, 2016 
Journal Title
 JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 
ISSN
 1051-0443 
Issue Date
2016
MeSH
Alanine Transaminase/blood ; Animals ; Antineoplastic Agents/administration & dosage* ; Antineoplastic Agents/blood ; Antineoplastic Agents/pharmacokinetics* ; Antineoplastic Agents/toxicity ; Aspartate Aminotransferases/blood ; Carcinoma, Hepatocellular/blood ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/therapy* ; Chemoembolization, Therapeutic/adverse effects ; Chemoembolization, Therapeutic/methods* ; Ethiodized Oil/administration & dosage ; Feasibility Studies ; Hypoxia-Inducible Factor 1, alpha Subunit/blood ; Liver Neoplasms, Experimental/blood ; Liver Neoplasms, Experimental/pathology ; Liver Neoplasms, Experimental/therapy* ; Male ; Necrosis ; Niacinamide/administration & dosage ; Niacinamide/analogs & derivatives* ; Niacinamide/pharmacokinetics ; Niacinamide/toxicity ; Phenylurea Compounds/administration & dosage* ; Phenylurea Compounds/pharmacokinetics* ; Phenylurea Compounds/toxicity ; Protein Kinase Inhibitors/administration & dosage* ; Protein Kinase Inhibitors/blood ; Protein Kinase Inhibitors/pharmacokinetics* ; Protein Kinase Inhibitors/toxicity ; Rabbits ; Tissue Distribution ; Vascular Endothelial Growth Factor A/blood
Abstract
PURPOSE: To investigate feasibility, safety, and effect of transarterial chemoembolization using sorafenib on degree of tumor necrosis in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: New Zealand White rabbits (n = 20) with a VX2 tumor were divided into two groups; one group was treated with hepatic arterial administration of 0.5 mL ethiodized oil alone (Lipiodol; Guerbet, Aulnay-sous-Bois, France) (transarterial embolization with Lipiodol [TAE-L] group), and one group was treated with 0.5 mL ethiodized oil plus 10 mg sorafenib (transarterial embolization with sorafenib [TAE-S] group). Liquid chromatography tandem mass spectrometry was used to measure sorafenib concentration in peripheral blood and tissue. Hepatic enzymes, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1α (HIF-1α) were measured at 0, 24, and 72 hours after treatment. Histopathologic examination was performed to evaluate extent of tumor necrosis and normal parenchymal damage. RESULTS: Serum sorafenib concentration peaked at 2 hours after treatment. The mean tissue concentration was 406.8 times greater than the serum concentration. Aspartate aminotransferase and alanine aminotransferase levels were significantly elevated in the TAE-S group at 24 hours after treatment. Serum VEGF and HIF-1α concentrations were not significantly different between the TAE-L and TAE-S groups. Hepatic parenchymal damage was more severe in the TAE-S group. Mean fraction of tumor necrosis after treatment was significantly greater in the TAE-S group. CONCLUSIONS: Transarterial chemoembolization using sorafenib resulted in a high intrahepatic concentration of sorafenib. The degree of tumor necrosis was significantly greater in the TAE-S group compared with the TAE-L group, but more severe toxicity of normal liver tissue also occurred.
Full Text
http://www.sciencedirect.com/science/article/pii/S1051044316003833
DOI
10.1016/j.jvir.2016.02.032
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gyoung Min(김경민) ORCID logo https://orcid.org/0000-0001-6768-4396
Kim, Do Young(김도영)
Kim, Man Deuk(김만득) ORCID logo https://orcid.org/0000-0002-3575-5847
Kim, Se Hoon(김세훈)
Park, Sung Il(박성일)
Shin, Min Woo(신민우)
Shin, Won Seon(신원선)
Won, Jong Yun(원종윤) ORCID logo https://orcid.org/0000-0002-8237-5628
Lee, Do Yun(이도연)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151837
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