Carmen Gacchina Johnson1, Yiqing Tang2, Avi Beck1, Matthew R Dreher2, David L Woods1, Ayele H Negussie1, Danielle Donahue3, Elliot B Levy1, Sean L Willis2, Andrew L Lewis2, Bradford J Wood1, Karun V Sharma4. 1. Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 2. Biocompatibles UK Ltd, a BTG International group company, Farnham, United Kingdom. 3. Mouse Imaging Facility, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. 4. Center for Interventional Oncology, Radiology, and Imaging Sciences, Clinical Center and National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Department of Radiology, Georgetown University Hospital, Washington, DC; Department of Radiology and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC. Electronic address: kvsharma@cnmc.org.
Abstract
PURPOSE: To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo. MATERIALS AND METHODS: An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model. RESULTS: Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology. CONCLUSIONS: A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.
PURPOSE: To develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo. MATERIALS AND METHODS: An ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model. RESULTS:Lipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology. CONCLUSIONS: A simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.
Authors: Andrew L Lewis; Sean L Willis; Matthew R Dreher; Yiqing Tang; Koorosh Ashrafi; Bradford J Wood; Elliot B Levy; Karun V Sharma; Ayele H Negussie; Andrew S Mikhail Journal: Future Oncol Date: 2018-06-26 Impact factor: 3.404
Authors: Koorosh Ashrafi; Yiqing Tang; Hugh Britton; Orianne Domenge; Delphine Blino; Andrew J Bushby; Kseniya Shuturminska; Mark den Hartog; Alessandro Radaelli; Ayele H Negussie; Andrew S Mikhail; David L Woods; Venkatesh Krishnasamy; Elliot B Levy; Bradford J Wood; Sean L Willis; Matthew R Dreher; Andrew L Lewis Journal: J Control Release Date: 2017-02-08 Impact factor: 9.776
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Authors: Marcus Caine; Ting Chung; Hugh Kilpatrick; Zainab Bascal; Sean Willis; Yiqing Tang; Thierry de Baere; Matthew Dreher; Andrew Lewis Journal: Theranostics Date: 2019-07-28 Impact factor: 11.556
Authors: Ayele H Negussie; Quirina M B de Ruiter; Hugh Britton; Danielle R Donahue; Quentin Boffi; Young-Seung Kim; William F Pritchard; Chrit Moonen; Gert Storm; Andrew L Lewis; Bradford J Wood Journal: Sci Rep Date: 2021-01-12 Impact factor: 4.996
Authors: Andrew L Lewis; Matthew R Dreher; Vincent O'Byrne; David Grey; Marcus Caine; Anthony Dunn; Yiqing Tang; Brenda Hall; Kirk D Fowers; Carmen Gacchina Johnson; Karun V Sharma; Bradford J Wood Journal: J Mater Sci Mater Med Date: 2015-12-16 Impact factor: 3.896