Preparation of Radiopaque Drug-Eluting Beads for Transcatheter Chemoembolization

J Vasc Interv Radiol. 2016 Jan;27(1):117-126.e3. doi: 10.1016/j.jvir.2015.09.011. Epub 2015 Nov 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Chemoembolization, Therapeutic / instrumentation*
  • Disease Models, Animal
  • Doxorubicin / administration & dosage
  • Drug Carriers*
  • Ethiodized Oil / administration & dosage
  • Liver / diagnostic imaging
  • Liver Neoplasms, Experimental / diagnostic imaging
  • Liver Neoplasms, Experimental / therapy*
  • Microspheres*
  • Phantoms, Imaging
  • Rabbits
  • X-Ray Microtomography

Substances

  • Drug Carriers
  • Ethiodized Oil
  • Doxorubicin