title: Safety and efficacy compared between irinotecan-loaded microspheres HepaSphere and DC bead in a model of VX2 liver metastases in the rabbit.
abstract: OBJECTIVE
  To compare irinotecan-eluting HepaSphere (BioSphere Medical, Roissy-en-France, France) and DC Bead (Biocompatibles UK Ltd, London, United Kingdom) embolization microspheres for distribution in tumors, release properties, tolerance, and antitumor effects in a model of liver metastases in the rabbit.
  
  
  METHODS
  Multiple liver tumors were created by injection of a VX2 cell suspension in the portal vein of rabbits. After 2 weeks, embolization of the proper hepatic artery was performed with a fixed volume of bland HepaSphere (n = 5), irinotecan-loaded HepaSphere (n = 6), or irinotecan-loaded DC Bead (n = 5) microspheres. Untreated animals injected with VX2 cells served as control animals (n = 5). Plasma pharmacokinetics of irinotecan and its metabolite SN38 were assessed. Histopathology and gene expression analysis were performed 3 days after treatment.
  
  
  RESULTS
  Among all treated groups, there was no significant difference in liver enzymes or liver damage on histology. Irinotecan-loaded HepaSphere microspheres showed a faster release of drug than DC Bead microspheres leading to a twofold higher concentration of drug in plasma for HepaSphere microspheres. HepaSphere microspheres were less frequently found inside tumor nodules on histology than DC Bead microspheres (11% vs 48%, P < .001) because of their larger size. Tumor necrosis was significantly greater for rabbits given irinotecan-loaded HepaSphere microspheres (69% of total tumor surface) and rabbits given DC Bead microspheres (50% of total tumor surface) compared with control animals (24% of total tumor surface, P = .006 and P = .047).
  
  
  CONCLUSIONS
  HepaSphere and DC Bead microspheres loaded with irinotecan caused significant necrosis of tumor nodules in a model of VX2 liver metastases. This outcome was mostly due to irinotecan delivery rather than vascular occlusion by the microspheres and was greater for HepaSphere microspheres compared with DC Bead microspheres.
authors.affiliation: Archimmed, 12 rue Charles de Gaulle, 78350 Jouy-en-Josas, France.. Electronic address: julien.namur@archimmed.com.
authors.forename: Julien
authors.initials: J
authors.lastname: Namur
authors.affiliation: Archimmed, 12 rue Charles de Gaulle, 78350 Jouy-en-Josas, France.
authors.forename: Florentina
authors.initials: F
authors.lastname: Pascale
authors.affiliation: Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Archimmed, 12 rue Charles de Gaulle, 78350 Jouy-en-Josas, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Sterba
authors.affiliation: Archimmed, 12 rue Charles de Gaulle, 78350 Jouy-en-Josas, France.
authors.forename: Saida Homayra
authors.initials: SH
authors.lastname: Ghegediban
authors.affiliation: Archimmed, 12 rue Charles de Gaulle, 78350 Jouy-en-Josas, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Verret
authors.affiliation: Pharmacology and Drug Analysis Department, Gustave Roussy, Cancer Campus, Grand Paris, Villejuif, France.; Vectorology and Anticancerous Therapeutics, University Paris-Sud, Villejuif, France.
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.affiliation: Pharmacology and Drug Analysis Department, Gustave Roussy, Cancer Campus, Grand Paris, Villejuif, France.
authors.forename: Atmane
authors.initials: A
authors.lastname: Seck
authors.affiliation: Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Osuga
authors.affiliation: Departments of Pathology, AP-HP Hôpital Lariboisère, Paris, France.; University Diderot-Paris 7, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Wassef
authors.affiliation: Biosphere Medical, Roissy-en-France, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Reb
authors.affiliation: Departments of Neuroradiology, AP-HP Hôpital Lariboisère, Paris, France.; University Diderot-Paris 7, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Laurent
mesh_terms: D065767:Activation, Metabolic; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004337:Drug Carriers; D015972:Gene Expression Regulation, Neoplastic; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D000077146:Irinotecan; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008863:Microspheres; D009336:Necrosis; D010316:Particle Size; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D000077146:Irinotecan; D002166:Camptothecin