title: In vivo evaluation of irinotecan-loaded QuadraSphere microspheres for use in chemoembolization of VX2 liver tumors.
abstract: OBJECTIVE
  To investigate the pharmacokinetics and chemoembolization efficacy of irinotecan-loaded QuadraSphere microspheres (QSMs) in a rabbit VX2 liver tumor model.
  
  
  METHODS
  Fourteen rabbits with VX2 liver tumors were divided into two groups. In the irinotecan-loaded QSM group (n = 7), 3 mg of QSMs (30-60 μm) containing 12 mg of irinotecan (0.6 mL; 20 mg/mL) were injected into the left hepatic artery. In the control group (hepatic arterial infusion [HAI] and QSMs; n = 7), 3 mg of QSMs suspended in ioxaglic acid were injected following a bolus injection of 0.6 mL of irinotecan solution (20 mg/mL). Sequential irinotecan, SN-38, and SN-38G concentration changes were measured in plasma within 24 hours and at 1 week and in tissues at 1 week. The VX2 tumor growth rates at 1 and 2 weeks were calculated from computed tomographic images.
  
  
  RESULTS
  All rabbits underwent successful embolization. Plasma irinotecan, SN-38, and SN-38G concentrations in the irinotecan-loaded QSM group showed significantly sustained release compared with the control group (P = .01). Compared with the control group, the irinotecan-loaded QSM group had significantly higher irinotecan concentration in liver tumors (P = .03) and a tendency toward higher SN-38 concentration in liver tumors (P = .29). The SN-38G tissue concentrations were below the limits of quantification. The tumor growth rate was significantly lower and the tumor necrosis rate significantly higher in the irinotecan-loaded QSM group (P = .02 and P = .01, respectively).
  
  
  CONCLUSIONS
  Chemoembolization via irinotecan-loaded QSMs more effectively suppresses tumor growth than chemoembolization with unloaded QSMs after HAI. A clinical feasibility study is warranted.
authors.affiliation: Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka. Electronic address: ushuika@yahoo.co.jp.
authors.forename: Kaishu
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka.
authors.forename: Noboru
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka.
authors.forename: Keigo
authors.initials: K
authors.lastname: Osuga
authors.affiliation: Department of Veterinary Surgery, Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Veterinary Surgery, Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Osaka.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Hori
authors.affiliation: Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kishimoto
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Osaka.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of Veterinary Surgery, Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Ohashi
authors.affiliation: Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tomiyama
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D000077146:Irinotecan; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000628:therapy*; D008863:Microspheres; D011817:Rabbits; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin