Gyoung Min Kim1, Man Deuk Kim2, Do Young Kim3, Se Hoon Kim4, Jong Yun Won1, Sung Il Park1, Do Yun Lee1, Wonseon Shin1, Minwoo Shin1. 1. 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. 2. 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. 3. 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. 4. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Shinchon-dong, Seodaemun-gu, Seoul 03722, Republic of Korea.
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.
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.
Authors: Fuad Nurili; Sebastien Monette; Adam O Michel; Achiude Bendet; Olca Basturk; Gokce Askan; Christopher Cheleuitte-Nieves; Hooman Yarmohammadi; Aaron W P Maxwell; Etay Ziv; Kyle M Schachtschneider; Ron C Gaba; Lawrence B Schook; Stephen B Solomon; F Edward Boas Journal: J Vasc Interv Radiol Date: 2021-01-23 Impact factor: 3.464