Ethiodized oil uptake does not predict doxorubicin drug delivery after chemoembolization in VX2 liver tumors

J Vasc Interv Radiol. 2012 Feb;23(2):265-73. doi: 10.1016/j.jvir.2011.10.022. Epub 2011 Dec 16.

Abstract

Purpose: To investigate the accuracy of ethiodized oil as an imaging marker of chemotherapy drug delivery after liver tumor chemoembolization in an animal model of hepatocellular carcinoma.

Materials and methods: Eleven VX2 liver tumors (mean diameter, 1.9 cm ± 0.4) in six New Zealand White rabbits were treated with chemoembolization using ethiodized oil and doxorubicin emulsion, followed by immediate euthanasia. Postprocedure noncontrast computed tomography (CT) was used to evaluate intratumoral ethiodized oil distribution and calculate iodine content within four peripheral tumor quadrants and the tumor core at a central tumor slice (N = 55 total tumor sections). Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was then used to directly measure doxorubicin concentration in the same tissue sections. Statistical correlation was performed between tissue iodine content and doxorubicin concentration by using linear regression.

Results: Chemoembolization was successfully performed in all tumors via the left or proper hepatic artery. A mean of 0.9 mL ± 0.6 ethiodized oil and 1.8 mg ± 1.2 doxorubicin were injected. CT-calculated tissue iodine content averaged 335 mg/mL ± 218. Corresponding LC-MS/MS analysis yielded a mean doxorubicin concentration of 15.8 μg/mL ± 14.3 in each sample. Although iodine content (391 mg/mL vs 112 mg/mL; P = .000) and doxorubicin concentration (18.0 μg/mL vs 7.2 μg/mL; P = .023) were significantly greater along peripheral tumor sections compared with the tumor core, no significant predictable correlation was evident between these measures (R(2) = 0.0099).

Conclusions: Tissue ethiodized oil content is a poor quantitative predictor of local doxorubicin concentration after liver tumor chemoembolization. Future studies should aim to identify a better imaging marker for chemoembolization drug delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / therapeutic use
  • Cell Line, Tumor
  • Chemoembolization, Therapeutic / methods*
  • Doxorubicin / pharmacokinetics*
  • Doxorubicin / therapeutic use*
  • Drug Carriers
  • Iodized Oil*
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism*
  • Male
  • Metabolic Clearance Rate
  • Rabbits
  • Radiography
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Iodized Oil
  • Doxorubicin