Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May;12(5):1105-1117.
doi: 10.1007/s13346-021-00985-8. Epub 2021 Apr 16.

Conventional versus drug-eluting embolic transarterial chemoembolization with doxorubicin: comparative drug delivery, pharmacokinetics, and treatment response in a rabbit VX2 tumor model

Ron C Gaba  1 , Ramzy C Khabbaz  2 , Ruth N Muchiri  3 , Joseph D Morrison  4 , Lobna Elkhadragy  2 , William M Totura  2 , Jonathan P Samuelson  5 , Herbert E Whiteley  5 , Ryan L Deaton  6 , Peter L Nguyen  6 , Maria Sverdlov  6 , Jeremy J Johnson  7 , Richard B van Breemen  3 , R Peter Lokken  8
Affiliations

Conventional versus drug-eluting embolic transarterial chemoembolization with doxorubicin: comparative drug delivery, pharmacokinetics, and treatment response in a rabbit VX2 tumor model

Ron C Gaba et al. Drug Deliv Transl Res. 2022 May.

Abstract

The purpose of this study was to compare intra-tumoral drug delivery, pharmacokinetics, and treatment response after doxorubicin (DOX) conventional (c-) versus drug-eluting embolic (DEE-) transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor model. Twenty-four rabbits with solitary liver tumors underwent c-TACE (n = 12) (1:2 water-in-oil emulsion, 0.6 mL volume, 2 mg DOX) or DEE-TACE (n = 12) (130,000 70-150 µm 2 mg DOX-loaded microspheres). Systemic, intra-tumoral, and liver DOX levels were measured using mass spectrometry up to 7-day post-procedure. Intra-tumoral DOX distribution was quantified using fluorescence imaging. Percent tumor necrosis was quantified by a pathologist blinded to treatment group. Lobar TACE was successfully performed in all cases. Peak concentration (CMAX, µg/mL) for plasma, tumor tissue, and liver were 0.666, 4.232, and 0.270 for c-TACE versus 0.103, 8.988, and 0.610 for DEE-TACE. Area under the concentration versus time curve (AUC, µg/mL ∗ min) for plasma, tumor tissue, and liver were 18.3, 27,078.8, and 1339.1 for c-TACE versus 16.4, 26,204.8, and 1969.6 for DEE-TACE. A single dose of intra-tumoral DOX maintained cytotoxic levels through 7-day post-procedure for both TACE varieties, with a half-life of 1.8 (c-TACE) and 0.8 (DEE-TACE) days. Tumor-to-normal liver DOX ratio was high (c-TACE, 20.2; DEE-TACE, 13.3). c-TACE achieved significantly higher DOX coverage of tumor vs. DEE-TACE (10.8% vs. 2.3%; P = 0.003). Percent tumor necrosis was similar (39% vs. 37%; P = 0.806). In conclusion, in a rabbit VX2 liver tumor model, both c-TACE and DEE-TACE achieved tumoricidal intra-tumoral DOX levels and high tumor-to-normal liver drug ratios, though c-TACE resulted in significantly greater tumor coverage.

Keywords: Animal model; Doxorubicin; Drug delivery; Pharmacokinetics; Transarterial chemoembolization.

PubMed Disclaimer

References

    1. Malagari K, Pomoni M, Kelekis A, Pomoni A, Dourakis S, Spyridopoulos T, et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2010;33(3):541–51. - DOI
    1. Shi M, Lu LG, Fang WQ, Guo RP, Chen MS, Li Y, et al. Roles played by chemolipiodolization and embolization in chemoembolization for hepatocellular carcinoma: single-blind, randomized trial. J Natl Cancer Inst. 2013;105(1):59–68. - DOI
    1. Johnson PJ, Kalayci C, Dobbs N, Raby N, Metivier EM, Summers L, et al. Pharmacokinetics and toxicity of intraarterial adriamycin for hepatocellular carcinoma: effect of coadministration of lipiodol. J Hepatol. 1991;13(1):120–7. - DOI
    1. Raoul JL, Heresbach D, Bretagne JF, Ferrer DB, Duvauferrier R, Bourguet P, et al. Chemoembolization of hepatocellular carcinomas. A study of the biodistribution and pharmacokinetics of doxorubicin. Cancer. 1992;70(3):585–90.
    1. Namur J, Wassef M, Millot JM, Lewis AL, Manfait M, Laurent A. Drug-eluting beads for liver embolization: concentration of doxorubicin in tissue and in beads in a pig model. J Vasc Interv Radiol. 2010;21(2):259–67. - DOI

Publication types

LinkOut - more resources