Transarterial embolization with sorafenib in animal livers: a pharmacokinetics study.
OBJECTIVE
To assess the safety and feasibility of the targeted delivery of the antiangiogenic drug sorafenib to the liver using transarterial chemoembolization methodology as a novel approach to hepatocellular carcinoma (HCC) therapy.


METHODS
Seven healthy New Zealand white rabbits were used in the study. After placement of a catheter in the common hepatic artery, six rabbits were treated with chemoembolization of sorafenib in iodized oil (Lipiodol) (sorafenib dose 0.1 mg/kg), and one rabbit received Lipiodol only. Liquid chromatography tandem mass spectrometry was used to measure the concentration of sorafenib in the peripheral blood and liver tissue 24 hours and 72 hours after treatment. Histochemical staining of the liver sections and biochemical measurements were performed.


RESULTS
The administration of sorafenib in Lipiodol emulsions by transarterial chemoembolization resulted in sorafenib concentrations of 794 ng/g ± 240 and 64 ng/g ± 15 in the liver tissue 24 hours and 72 hours after treatment. The average liver-to-serum ratios 24 hours and 72 hours after treatment were approximately 14 and 22. The histochemical staining of the liver tissue sections and aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase and total bilirubin concentrations indicated no significant liver damage.


CONCLUSIONS
Transarterial chemoembolization with sorafenib in Lipiodol is an effective methodology for the localized delivery of this drug to the liver and has possible practical implications in therapeutic interventions for the treatment of hepatocellular carcinoma.
1st and 2nd Departments of Radiology, University of Athens, Athens.
Achilleas N
AN
Chatziioannou
Alexandros P
AP
Siskos
Dionisios
D
Loxas
Nikolaos
N
Kavatzas
Georgios
G
Agrogiannis
Demosthenes
D
Fokas
Katerina
K
Malagari
Nikolaos G
NG
Kostomitsopoulos
Olga
O
Tsigkou
Constantin
C
Tamvakopoulos
D000410:Alanine Transaminase / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004998:Ethiodized Oil / Q000008:administration & dosage; D005240:Feasibility Studies; D006499:Hepatic Artery; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D023421:Models, Animal; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D000077157:Sorafenib; D053719:Tandem Mass Spectrometry; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D009536:Niacinamide; D004998:Ethiodized Oil; D000077157:Sorafenib; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D001663:Bilirubin
ALT; AST; AcCN; GGT; HCC; LC-ESI-MS/MS; LC-MS/MS; acetonitrile; alanine aminotransferase; aspartate aminotransferase; hepatocellular carcinoma; liquid chromatography electrospray ionization mass spectrometry; liquid chromatography tandem mass spectrometry; γ-glutamyltransferase