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Transarterial embolization with sorafenib in animal livers: a pharmacokinetics study
Achilleas N Chatziioannou1, Alexandros P Siskos, Dionisios Loxas
11st and 2nd Departments of Radiology, University of Athens, Athens.
Purpose:
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.
Materials And 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.
Insights
Transarterial chemoembolization safely delivers sorafenib to the liver for hepatocellular carcinoma (HCC) therapy. This localized drug delivery method shows promise for HCC treatment, with minimal liver damage observed.
Area of Science:
- Hepatobiliary Medicine
- Oncology
- Interventional Radiology
Background:
- Hepatocellular carcinoma (HCC) is a primary liver cancer with limited treatment options.
- Sorafenib is an antiangiogenic drug used in HCC therapy.
- Targeted drug delivery aims to improve efficacy and reduce systemic toxicity.
Purpose of the Study:
- To evaluate the safety and feasibility of targeted sorafenib delivery to the liver.
- To assess the efficacy of transarterial chemoembolization (TACE) for sorafenib delivery in HCC treatment.
Main Methods:
- Seven New Zealand white rabbits underwent TACE with sorafenib in Lipiodol.
- Sorafenib concentrations in liver tissue and peripheral blood were measured.
- Liver damage was assessed via histochemical staining and biochemical markers.
Main Results:
- High sorafenib concentrations were achieved in liver tissue post-TACE.
- Favorable liver-to-serum sorafenib ratios were observed.
- No significant liver damage was indicated by histochemical and biochemical analyses.
Conclusions:
- TACE with sorafenib in Lipiodol enables effective localized drug delivery to the liver.
- This method holds potential for improved hepatocellular carcinoma (HCC) therapeutic interventions.
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