title: Development and Validation of Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin: Preclinical Study.
abstract: To develop a novel endovascular chemotherapy filter (CF) able to remove excess drug from the blood during intra-arterial chemotherapy delivery (IAC), thus preventing systemic toxicities and thereby enabling higher dose IAC. A flow circuit containing 2.5 mL of ion-exchange resin was constructed. Phosphate-buffered saline (PBS) containing 50 mg doxorubicin (Dox) was placed in the flow model with the hypothesis that doxorubicin would bind rapidly to resin. To simulate IAC, 50 mg of doxorubicin was infused over 10 min into the flow model containing resin. Similar testing was repeated with porcine serum. Doxorubicin concentrations were measured over 60 min and compared to controls (without resin). Single-pass experiments were also performed. Based on these experiments, an 18F CF was constructed with resin in its tip. In a pilot porcine study, the device was deployed under fluoroscopy. A control hepatic doxorubicin IAC model (no CF placed) was developed in another animal. A second CF device was created with a resin membrane and tested in the infrarenal inferior vena cava (IVC) of a swine. In the PBS model, resin bound 76% of doxorubicin in 10 min, and 92% in 30 min (P<0.001). During IAC simulation, 64% of doxorubicin bound in 10 min and 96% in 60 min (P<0.001). On average, 51% of doxorubicin concentration was reduced during each pass in single pass studies. In porcine serum, 52% of doxorubicin bound in 10 min, and 80% in 30 min (P<0.05). CF device placement and administration of IAC were successful in three animals. No clot was present on the resin within the CF following the in vivo study. The infrarenal IVC swine study demonstrated promising results with up to 85% reduction in peak concentration by the CF device. An endovascular CF device was developed and shown feasible in vitro. An in vivo model was established with promising results supporting high-capacity rapid doxorubicin filtration from the blood that can be further evaluated in future studies.
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , 185 Berry Street, Suite 350, San Francisco, CA 94107-5705 e-mail:  anand.patel@ucsf.edu.
authors: Anand S
authors: AS
authors: Patel
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Maythem
authors: M
authors: Saeed
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Erin J
authors: EJ
authors: Yee
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Jeffrey
authors: J
authors: Yang
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Gregory J
authors: GJ
authors: Lam
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Aaron D
authors: AD
authors: Losey
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Prasheel V
authors: PV
authors: Lillaney
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Bradford
authors: B
authors: Thorne
authors: ChemoFilter, Inc. , 645 Woodstock Road, Hillsborough, CA 94010.
authors: Albert K
authors: AK
authors: Chin
authors: ChemoFilter, Inc. , 645 Woodstock Road, Hillsborough, CA 94010.
authors: Sheena
authors: S
authors: Malik
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Mark W
authors: MW
authors: Wilson
authors: Materials Sciences Division, Lawrence Berkeley National Laboratory , Berkeley, CA 94720.
authors: Xi C
authors: XC
authors: Chen
authors: Materials Sciences Division, Lawrence Berkeley National Laboratory , Berkeley, CA 94720 ;
authors: Nitash P
authors: NP
authors: Balsara
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco , San Francisco, CA 94107.
authors: Steven W
authors: SW
authors: Hetts
keywords: interventional oncology; liver cancer; medical devices
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