Effect of bead size and doxorubicin loading on tumor cellular injury after transarterial embolization and chemoembolization in a rat model of hepatocellular carcinoma

Abstract

Embolic agents used in transarterial embolization for intermediate stage hepatocellular carcinoma reduce blood flow into tumors and can deliver anticancer drugs. Tumor blood supply can be interrupted using doxorubicin-eluting beads (DEB-TACE) or non-loaded beads (TAE) of different calibers. In this preclinical study, we characterized the extent of remaining stressed tumor cells after treatment, hypoxia within the surviving tumor regions, and inflammatory immune cell infiltrates after embolization with 40-60 or 70-150 μm with non-loaded or doxorubicin-loaded beads at 3 and 7 days after treatment. TAE-treated tumors had more stressed and surviving tumor cells after 3 days, irrespective of bead size, compared with DEB-TACE-treated tumors. Hypoxic stress of residual cells increased after treatment with 70-150 μm beads without or with doxorubicin. Treatment with DEB-TACE of 70-150 μm resulted in increased inflammation and proliferation in the adjacent parenchyma. Inflammatory cell infiltrates were reduced at the periphery of tumors treated with 40-60 μm DEB-TACE.