title: Improved drug targeting to liver tumors after intra-arterial delivery using superparamagnetic iron oxide and iodized oil: preclinical study in a rabbit model.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the feasibility and the therapeutic efficacy of a novel drug-delivery system that uses superparamagnetic iron oxide (SPIO) and iodized oil (IO) to improve the selective intra-arterial (IA) drug delivery to an experimentally induced hepatic tumor.
  
  
  METHODS
  This animal study was approved by our institutional animal care and use committee. Fifteen rabbits with hepatic VX2 carcinomas were treated with IA delivery of 4 different agents: doxorubicin alone (group A, n = 3), doxorubicin/IO (group B, n = 3), a doxorubicin/SPIO complex (group C, n = 4), and a doxorubicin/SPIO/IO complex (group D, n = 5). The infused doxorubicin dose was 1 mg for all groups. The serum doxorubicin concentration was measured at 0, 5, 30, 60, and 120 minutes after the delivery. To assess the distribution of the SPIO, magnetic resonance (MR) scans were performed at day 7 after the delivery, when computed tomographic scans were performed in addition to MR in group B and D to assess the distribution of IO. After the completion of follow-up imaging, all the animals were euthanized to measure the intratumoral doxorubicin concentration and to assess tumor viability through pathologic examination.
  
  
  RESULTS
  Groups C and D demonstrated significantly lower MR signal intensities, which inversely corresponded to SPIO deposition, in the tumor areas than did groups A and B. Group D exhibited the lowest serum doxorubicin concentration at all time points up to 180 minutes after the delivery, suggesting minimal passage of doxorubicin into the systemic circulation. The intratumoral doxorubicin concentrations were 72.4 ng/g for group A, 142.0 ng/g for group B, 264.1 ng/g for group C, and 679.6 ng/g for group D. The proportion of viable tumor cells were 65.3% for group A, 1.3% for group B, 17.0% for group C, and 0.1% for group D.
  
  
  CONCLUSIONS
  The drug-delivery system developed using SPIO and IO can result in better drug targeting when it is used for IA delivery to liver cancer. The results of this study warrant further investigation of this potential clinical treatment of advanced liver cancer.
authors.affiliation: From the *Department of Radiology, National Cancer Center, Goyang-si; †Engineering Research Institute, Department of Materials Science and Engineering, ‡Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, SNUMRC, Seoul, Republic of Korea.
authors.forename: In Joon
authors.initials: IJ
authors.lastname: Lee
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Ahn
authors.forename: Eui-Joon
authors.initials: EJ
authors.lastname: Cha
authors.forename: In Jae
authors.initials: IJ
authors.lastname: Chung
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Chung
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D007269:Injections, Intra-Arterial; D007459:Iodized Oil / Q000737:chemistry* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D053769:Nanocapsules / Q000737:chemistry* / Q000627:therapeutic use; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003911:Dextrans; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; C097921:ferumoxtran-10; D007459:Iodized Oil; D004317:Doxorubicin