title: Characterization of a novel intrinsically radiopaque Drug-eluting Bead for image-guided therapy: DC Bead LUMI™.
abstract: We have developed a straightforward and efficient method of introducing radiopacity into Polyvinyl alcohol (PVA)-2-Acrylamido-2-methylpropane sulfonic acid (AMPS) hydrogel beads (DC Bead™) that are currently used in the clinic to treat liver malignancies. Coupling of 2,3,5-triiodobenzaldehyde to the PVA backbone of pre-formed beads yields a uniformly distributed level of iodine attached throughout the bead structure (~150mg/mL) which is sufficient to be imaged under standard fluoroscopy and computed tomography (CT) imaging modalities used in treatment procedures (DC Bead LUMI™). Despite the chemical modification increasing the density of the beads to ~1.3g/cm3and the compressive modulus by two orders of magnitude, they remain easily suspended, handled and administered through standard microcatheters. As the core chemistry of DC Bead LUMI™ is the same as DC Bead™, it interacts with drugs using ion-exchange between sulfonic acid groups on the polymer and the positively charged amine groups of the drugs. Both doxorubicin (Dox) and irinotecan (Iri) elution kinetics for all bead sizes evaluated were within the parameters already investigated within the clinic for DC Bead™. Drug loading did not affect the radiopacity and there was a direct relationship between bead attenuation and Dox concentration. The ability (Dox)-loaded DC Bead LUMI™ to be visualized in vivo was demonstrated by the administration of into hepatic arteries of a VX2 tumor-bearing rabbit under fluoroscopy, followed by subsequent CT imaging.
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley GU15 3YL, UK.
authors.forename: Koorosh
authors.initials: K
authors.lastname: Ashrafi
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley GU15 3YL, UK.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley GU15 3YL, UK.
authors.forename: Hugh
authors.initials: H
authors.lastname: Britton
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley GU15 3YL, UK.
authors.forename: Orianne
authors.initials: O
authors.lastname: Domenge
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley GU15 3YL, UK.
authors.forename: Delphine
authors.initials: D
authors.lastname: Blino
authors.affiliation: School of Engineering and Materials Science, Queen Mary University, Mile End Road, London, E1 4NS, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bushby
authors.affiliation: School of Engineering and Materials Science, Queen Mary University, Mile End Road, London, E1 4NS, UK.
authors.forename: Kseniya
authors.initials: K
authors.lastname: Shuturminska
authors.affiliation: iXR, Philips Healthcare, Best, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: den Hartog
authors.affiliation: iXR, Philips Healthcare, Best, The Netherlands.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Radaelli
authors.affiliation: The Center for Interventional Oncology Radiology and Imaging Sciences, Clinical Center, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Bethesda, MD, USA.
authors.forename: Ayele H
authors.initials: AH
authors.lastname: Negussie
authors.affiliation: The Center for Interventional Oncology Radiology and Imaging Sciences, Clinical Center, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Bethesda, MD, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Mikhail
authors.affiliation: The Center for Interventional Oncology Radiology and Imaging Sciences, Clinical Center, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Bethesda, MD, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Woods
authors.affiliation: The Center for Interventional Oncology Radiology and Imaging Sciences, Clinical Center, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Bethesda, MD, USA.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnasamy
authors.affiliation: The Center for Interventional Oncology Radiology and Imaging Sciences, Clinical Center, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Bethesda, MD, USA.
authors.forename: Elliot B
authors.initials: EB
authors.lastname: Levy
authors.affiliation: The Center for Interventional Oncology Radiology and Imaging Sciences, Clinical Center, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10, Bethesda, MD, USA.
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley GU15 3YL, UK.
authors.forename: Sean L
authors.initials: SL
authors.lastname: Willis
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley GU15 3YL, UK.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley GU15 3YL, UK. Electronic address: andrew.lewis@btgplc.com.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001547:Benzaldehydes / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers; D065546:Drug Liberation; D005260:Female; D006801:Humans; D007462:Iodobenzenes / Q000737:chemistry; D007474:Ion Exchange; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy; D008863:Microspheres; D061848:Optical Imaging; D010316:Particle Size; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011817:Rabbits; D013499:Surface Properties; D014057:Tomography, X-Ray Computed
chemical_list: C000625931:2,3,5-triiodobenzaldehyde; D000970:Antineoplastic Agents; D001547:Benzaldehydes; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007462:Iodobenzenes; D000077146:Irinotecan; D004317:Doxorubicin; D011142:Polyvinyl Alcohol; D002166:Camptothecin
keywords: Controlled drug release; Radiopaque Drug-eluting Beads; Transarterial chemoembolization; X-ray imaging