Endovascular ion exchange chemofiltration device reduces off-target doxorubicin exposure in a hepatic intra-arterial chemotherapy model

Colin Yee, David McCoy, Jay Yu, Aaron Losey, Caroline Jordan, Terilyn Moore, Carol Stillson, Hee Jeung Oh, Bridget Kilbride, Shuvo Roy, Anand Patel, Mark W. Wilson, Steven W. Hetts

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Purpose: To determine if endovascular chemofiltration with an ionic device (ChemoFilter [CF]) can be used to reduce systemic exposure and off-target biodistribution of doxorubicin (DOX) during hepatic intra-arterial chemotherapy (IAC) in a preclinical model. Materials and Methods: Hepatic IAC infusions were performed in six pigs with normal livers. Animals underwent two 10-minute intra-arterial infusions of DOX (200 mg) into the common hepatic artery. Both the treatment group and the control group received initial IAC at 0 minutes and a second dose at 200 minutes. Prior to the second dose, CF devices were deployed in and adjacent to the hepatic venous outflow tract of treatment animals. Systemic exposure to DOX was monitored via blood samples taken during IAC procedures. After euthanasia, organ tissue DOX concentrations were analyzed. Alterations in systemic DOX exposure and biodistribution were compared by using one-tailed t tests. Results: CF devices were well tolerated, and no hemodynamic, thrombotic, or immunologic complications were observed. Animals treated with a CF device had a significant reduction in systemic exposure when compared with systemic exposure in the control group (P <.009). Treatment with a CF device caused a significant decrease in peak DOX concentration (31%, P <.01) and increased the time to maximum concentration (P <.03). Tissue analysis was used to confirm significant reduction in DOX accumulation in the heart and kidneys (P <.001 and P <.022, respectively). Mean tissue concentrations in the heart, kidneys, and liver of animals treated with CF compared with those in control animals were 14.2 mg/g ± 1.9 (standard deviation) versus 26.0 mg/g ± 1.8, 46.4 mg/g ± 4.6 versus 172.6 mg/g ± 40.2, and 217.0 mg/g ± 5.1 versus 236.8 mg/g ± 9.0, respectively. Fluorescence imaging was used to confirm in vivo DOX binding to CF devices. Conclusion: Reduced systemic exposure and heart bioaccumulation of DOX during local-regional chemotherapy to the liver can be achieved through in situ adsorption by minimally invasive image-guided CF devices.

Original languageEnglish (US)
Article numbere190009
JournalRadiology: Imaging Cancer
Volume1
Issue number1
DOIs
StatePublished - Sep 2019

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging
  • Oncology

Fingerprint

Dive into the research topics of 'Endovascular ion exchange chemofiltration device reduces off-target doxorubicin exposure in a hepatic intra-arterial chemotherapy model'. Together they form a unique fingerprint.

Cite this