Purpose To test the feasibility of targeted intra-arterial 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 ± 0.2 kg) were treated with chemoembolization using sorafenib and ethiodized oil emulsion, followed by immediate euthanasia. Post-procedure 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. Histopathological 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 mL, 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. Histopathological assessment showed only mild or moderate non-specific ballooning degeneration in zone 3 hepatocytes, without tissue necrosis. Conclusions Targeted transarterial sorafenib delivery is feasible and results in higher tissue drug levels than that reported for systemic sorafenib therapy, without immediate histopathological tissue toxicity. Future studies should aim to determine the utility of sorafenib chemoembolization in reducing hypoxia-induced vasculogenesis in liver tumors.

Purpose-To test the feasibility of targeted intra-arterial 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 ± 0.2 kg) were treated with chemoembolization using sorafenib and ethiodized oil emulsion, followed by immediate euthanasia. Post-procedure 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. Histopathological 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 mL, 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. Histopathological assessment showed only mild or moderate non-specific ballooning degeneration in zone 3 hepatocytes, without tissue necrosis.Conclusions-Targeted transarterial sorafenib delivery is feasible and results in higher tissue drug levels than that reported for systemic sorafenib therapy, without immediate histopathological tissue toxicity. Future studies should aim to determine the utility of sorafenib chemoembolization in reducing hypoxia-induced vasculogenesis in liver tumors.

No abstract

No abstract

Supplemental Digital Content is Available in the Text.

No abstract

No abstract

No abstract