title: Synthesis and characterization of image-able polyvinyl alcohol microspheres for image-guided chemoembolization.
abstract: Therapeutic embolization of blood vessels is a minimally invasive, catheter-based procedure performed with solid or liquid emboli to treat bleeding, vascular malformations, and vascular tumors. Hepatocellular carcinoma (HCC) affects about half a million people per year. When unresectable, HCC is treated with embolization and local drug therapy by transarterial chemoembolization (TACE). For TACE, drug eluting beads (DC Bead(®)) may be used to occlude or reduce arterial blood supply and deliver chemotherapeutics locally to the tumor. Although this treatment has been shown to be safe and to improve patient survival, the procedure lacks imaging feedback regarding the location of embolic agent and drug coverage. To address this shortcoming, herein we report the synthesis and characterization of image-able drug eluting beads (iBeads) from the commercial DC Bead(®) product. Two different radiopaque beads were synthesized. In one approach, embolic beads were conjugated with 2,3,5-triiodobenzyl alcohol in the presence of 1,1'-carbonyldiimidazol to give iBead I. iBead II was synthesized with a similar approach but instead using a trimethylenediamine spacer and 2,3,5-triiodobenzoic acid. Doxorubicin was loaded into the iBeads II using a previously reported method. Size and shape of iBeads were evaluated using an upright microscope and their conspicuity assessed using a clinical CT and micro-CT. Bland and Dox-loaded iBeads II visualized with both clinical CT and microCT. Under microCT, individual bland and Dox loaded beads had a mean attenuation of 7904 ± 804 and 11,873.96 ± 706.12 HU, respectively. These iBeads have the potential to enhance image-guided TACE procedures by providing localization of embolic-particle and drug.
authors.affiliation: Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, 20814, USA, negussiea@cc.nih.gov.
authors.forename: Ayele H
authors.initials: AH
authors.lastname: Negussie
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
authors.forename: Carmen Gacchina
authors.initials: CG
authors.lastname: Johnson
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Tang
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Karun V
authors.initials: KV
authors.lastname: Sharma
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000628:therapy; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy; D008422:Materials Testing; D008863:Microspheres; D019047:Phantoms, Imaging; D011142:Polyvinyl Alcohol / Q000737:chemistry; D014283:Triiodobenzoic Acids / Q000737:chemistry; D055114:X-Ray Microtomography
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003287:Contrast Media; D003959:Diamines; D004337:Drug Carriers; D014283:Triiodobenzoic Acids; D004317:Doxorubicin; D011142:Polyvinyl Alcohol; C009475:trimethylenediamine; C052968:2,3,5-triiodobenzoic acid