title: DC BeadM1™: towards an optimal transcatheter hepatic tumour therapy.
abstract: Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1 (TM), 70-150 μm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and drug dose delivered. Both unloaded and drug loaded DC BeadM1 were shown to have a greater density of distal volume of penetration although the ultimate distal level of penetration was the same as that of the 100-300 µm beads in an in vitro penetration model. Elution of doxorubicin was slower than irinotecan elution, but it was similar when comparing the same drug elution from 70 to 150 µm compared to 100-300 µm beads. Radiopaque versions of 70-150 and 100-300 µm beads were prepared in order to evaluate distribution ex vivo using µ-CT and doxorubicin distribution using epifluorescent microscopy. Liver distribution of the radiopaque versions of the beads was shown to be more distal and efficient at filling smaller vessels with the DC BeadM1 and correspondingly more beads were found per vessel histologically with a larger area of drug coverage with the smaller size range. This study indicates that the smaller (70-150 μm) beads should permit an increased dose of drug to be administered to both hypervascular and hypovascular tumours as compared to 100-300 µm beads.
authors.affiliation: Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK. andrew.lewis@biocompatibles.com.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
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.
authors.forename: Vincent
authors.initials: V
authors.lastname: O'Byrne
authors.affiliation: Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK.
authors.forename: David
authors.initials: D
authors.lastname: Grey
authors.affiliation: Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Caine
authors.affiliation: Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Dunn
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: Brenda
authors.initials: B
authors.lastname: Hall
authors.affiliation: Biocompatibles UK Ltd, a BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, UK.
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Fowers
authors.affiliation: Center for Interventional Oncology, Department of Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carmen Gacchina
authors.initials: CG
authors.lastname: Johnson
authors.affiliation: Center for Interventional Oncology, Department of Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.|Children's National Medical Center, 1630 Euclid Street NW#1, Washington, DC, USA.
authors.forename: Karun V
authors.initials: KV
authors.lastname: Sharma
authors.affiliation: Center for Interventional Oncology, Department of Radiology & Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D057785:Catheters; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D000077146:Irinotecan; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D011817:Rabbits; D055114:X-Ray Microtomography
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D000077146:Irinotecan; D004317:Doxorubicin; D002166:Camptothecin