Transarterial Chemoembolization in a Woodchuck Model of Hepatocellular Carcinoma

J Vasc Interv Radiol. 2020 May;31(5):812-819.e1. doi: 10.1016/j.jvir.2019.08.031. Epub 2020 Feb 24.

Abstract

Purpose: To assess the feasibility of transarterial chemoembolization with drug-eluting embolic (DEE) microspheres in a woodchuck model of hepatocellular carcinoma (HCC).

Materials and methods: Nine woodchucks were studied: 4 normal animals and 5 animals infected with woodchuck hepatitis virus in which HCC had developed. Three animals with HCC underwent multidetector CT. A 3-F sheath was introduced into the femoral artery, and the hepatic arteries were selectively catheterized with 2.0-2.4-F microcatheters. Normal animals underwent diagnostic angiography and bland embolization. Animals with HCC underwent DEE transarterial chemoembolization with 70-150-μm radiopaque microspheres loaded with 37.5 mg doxorubicin per milliliter. Cone-beam CT and multidetector CT were performed. Following euthanasia, explanted livers underwent micro-CT, histopathologic examination, and fluorescence imaging of doxorubicin.

Results: The tumors were hypervascular and supplied by large-caliber tortuous vessels, with arteriovenous shunts present in 2 animals. There was heterogeneous enhancement on multidetector CT with areas of necrosis. Six tumors were identified. The most common location was the right medial lobe (n = 3). Mean tumor volume was 30.7 cm3 ± 12.3. DEE chemoembolization of tumors was achieved. Excluding the 2 animals with arteriovenous shunts, the mean volume of DEE microspheres injected was 0.49 mL ± 0.17. Fluorescence imaging showed diffusion of doxorubicin from the DEE microspheres into the tumor.

Conclusions: Woodchuck HCC shares imaging appearances and biologic characteristics with human HCC. Selective catheterization and DEE chemoembolization may similarly be performed. Woodchucks may be used to model interventional therapies and possibly characterize radiologic-pathologic correlations.

MeSH terms

  • Angiography, Digital Subtraction
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Carcinoma, Hepatocellular / virology
  • Chemoembolization, Therapeutic*
  • Cone-Beam Computed Tomography
  • Disease Models, Animal
  • Doxorubicin / administration & dosage*
  • Female
  • Hepatitis B / complications
  • Hepatitis B / virology
  • Hepatitis B Virus, Woodchuck / pathogenicity
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Liver Neoplasms / virology
  • Male
  • Marmota
  • Microscopy, Fluorescence
  • Microspheres
  • Multidetector Computed Tomography
  • Tumor Burden

Substances

  • Antibiotics, Antineoplastic
  • Doxorubicin