title: Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect.
abstract: OBJECTIVE
  To investigate feasibility, safety, and effect of transarterial chemoembolization using sorafenib on degree of tumor necrosis in a rabbit VX2 liver tumor model.
  
  
  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.
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Gyoung Min
authors.initials: GM
authors.lastname: Kim
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea. Electronic address: mdkim@yuhs.ac.
authors.forename: Man Deuk
authors.initials: MD
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Do Young
authors.initials: do Y
authors.lastname: Kim
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Jong Yun
authors.initials: JY
authors.lastname: Won
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Park
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Do Yun
authors.initials: do Y
authors.lastname: Lee
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Wonseon
authors.initials: W
authors.lastname: Shin
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
authors.forename: Minwoo
authors.initials: M
authors.lastname: Shin
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects / Q000379:methods*; D004998:Ethiodized Oil / Q000008:administration & dosage; D005240:Feasibility Studies; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000473:pathology / Q000628:therapy*; D008297:Male; D009336:Necrosis; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D011817:Rabbits; D000077157:Sorafenib; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D004998:Ethiodized Oil; D000077157:Sorafenib; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase