Transarterial sorafenib chemoembolization: Preliminary study of technical feasibility in a rabbit model

Ron C. Gaba, Felix Y. Yap, Elizabeth M. Martinez, Yongchao Li, Grace Guzman, Ahmad Parvinian, Richard B. Van Breemen, Nishant Kumar

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Purpose: To test the feasibility of targeted intraarterial administration of the tyrosine kinase inhibitor chemotherapeutic agent sorafenib to inhibit embolotherapy-induced tumor angiogenesis and reduce systemic drug side effects. Materials and Methods: The left hepatic lobes of five New Zealand White rabbits (mean weight, 2.7 kg±0.2) were treated with chemoembolization with sorafenib and ethiodized oil emulsion, followed by immediate euthanasia. Postprocedure noncontrast computed tomography (CT) was used to evaluate intrahepatic chemotherapy mixture distribution. Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was then used to directly measure sorafenib concentration in the treated liver tissue. Histopathologic assessment of treated left lobes was performed to identify any immediate toxic effects of the sorafenib solution. Results: Lobar sorafenib chemoembolization was successfully performed in all cases via the left hepatic artery. Sorafenib and ethiodized oil (mean, 6.4 mg±3.8 and 0.95 mL±0.7, respectively) were injected, and CT confirmed targeted left hepatic lobe sorafenib emulsion delivery in all cases. Corresponding LC-MS/MS analysis yielded a mean sorafenib concentration of 94.2 μg/mL±48.3 in treated left lobe samples (n = 5), significantly greater than typical therapeutic drug levels (2-10 μg/mL) achieved with oral sorafenib systemic therapy. Histopathologic assessment showed only mild or moderate nonspecific ballooning degeneration in zone 3 hepatocytes, without tissue necrosis. Conclusions: Targeted transarterial sorafenib delivery is feasible and results in higher tissue drug levels than reported for systemic sorafenib therapy, without immediate histopathologic tissue toxicity. Future studies should aim to determine the utility of sorafenib chemoembolization in reducing hypoxia-induced vasculogenesis in liver tumors.

Original languageEnglish (US)
Pages (from-to)744-750
Number of pages7
JournalJournal of Vascular and Interventional Radiology
Volume24
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • C
  • HCC
  • HIF
  • LC-MS/MS
  • SRM
  • UHPLC
  • VEGF
  • VEGFR
  • hepatocellular carcinoma
  • hypoxia-inducible factor
  • liquid chromatography/tandem mass spectrometry
  • peak plasma concentration
  • selected reaction monitoring
  • ultra-high-pressure liquid chromatography
  • vascular endothelial growth factor
  • vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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