title: Image-guided thermal therapy with a dual-contrast magnetic nanoparticle formulation: A feasibility study.
abstract: The aim of this study was to develop and investigate the properties of a magnetic iron oxide nanoparticle-ethiodised oil formulation for image-guided thermal therapy of liver cancer.
  
  
  
  The formulation comprises bionised nano-ferrite (BNF) nanoparticles suspended in ethiodised oil, emulsified with polysorbate 20 (BNF-lip). Nanoparticle size was measured via photon correlation spectroscopy and transmission electron microscopy. In vivo thermal therapy capability was tested in two groups of male Foxn1(nu) mice bearing subcutaneous HepG2 xenograft tumours. Group I (n = 12) was used to screen conditions for group II (n = 48). In group II, mice received one of BNF-lip (n = 18), BNF alone (n = 16), or PBS (n = 14), followed by alternating magnetic field (AMF) hyperthermia, with either varied duration (15 or 20 min) or amplitude (0, 16, 20, or 24 kA/m). Image-guided fluoroscopic intra-arterial injection of BNF-lip was tested in New Zealand white rabbits (n = 10), bearing liver VX2 tumours. The animals were subsequently imaged with CT and 3 T MRI, up to 7 days post-injection. The tumours were histopathologically evaluated for distribution of BNF-lip.
  
  
  
  The BNF showed larger aggregate diameters when suspended in BNF-lip, compared to clear solution. The BNF-lip formulation produced maximum tumour temperatures with AMF >20 kA/m and showed positive X-ray visibility and substantial shortening of T1 and T2 relaxation time, with sustained intratumoural retention up to 7 days post-injection. On pathology, intratumoural BNF-lip distribution correlated well with CT imaging of intratumoural BNF-lip distribution.
  
  
  
  The BNF-lip formulation has favourable thermal and dual imaging capabilities for image-guided thermal therapy of liver cancer, suggesting further exploration for clinical applications.
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;
authors.forename: Anilchandra
authors.initials: A
authors.lastname: Attaluri
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;
authors.forename: Madhav
authors.initials: M
authors.lastname: Seshadri
authors.affiliation: b Department of Radiology and Radiological Sciences , Johns Hopkins Hospital , Baltimore , Maryland ;
authors.forename: Sahar
authors.initials: S
authors.lastname: Mirpour
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;
authors.forename: Michele
authors.initials: M
authors.lastname: Wabler
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;
authors.forename: Thomas
authors.initials: T
authors.lastname: Marinho
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;
authors.forename: Muhammad
authors.initials: M
authors.lastname: Furqan
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;
authors.forename: Haoming
authors.initials: H
authors.lastname: Zhou
authors.affiliation: c Center for Biological Evaluation and Research , Food and Drug Administration , Bethesda , Maryland , USA ;
authors.forename: Silvia
authors.initials: S
authors.lastname: De Paoli
authors.affiliation: d Micromod Partikeltechnologie, GmbH , Rostock , Germany ;
authors.forename: Cordula
authors.initials: C
authors.lastname: Gruettner
authors.affiliation: e Siemens Healthcare Solutions, Inc. , Baltimore , Maryland , USA ;
authors.forename: Wesley
authors.initials: W
authors.lastname: Gilson
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;
authors.forename: Theodore
authors.initials: T
authors.lastname: DeWeese
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;|f Department of Genetics and Morphology , Institute of Biological Sciences, University of Brasilia , Brazil ;
authors.forename: Monica
authors.initials: M
authors.lastname: Garcia
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences , Johns Hopkins University School of Medicine , Baltimore , Maryland ;|g Department of Oncology , Johns Hopkins University School of Medicine , Baltimore , Maryland ;|h Institute for NanoBioTechnology, Johns Hopkins University , Baltimore , Maryland ;|i Department of Materials Science and Engineering , Johns Hopkins University , Baltimore , Maryland , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ivkov
authors.affiliation: b Department of Radiology and Radiological Sciences , Johns Hopkins Hospital , Baltimore , Maryland ;
authors.forename: Eleni
authors.initials: E
authors.lastname: Liapi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004998:Ethiodized Oil / Q000008:administration & dosage / Q000627:therapeutic use; D005240:Feasibility Studies; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D006979:Hyperthermia, Induced; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D008819:Mice, Nude; D011136:Polysorbates / Q000008:administration & dosage / Q000627:therapeutic use; D011817:Rabbits; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D014463:Ultrasonography
chemical_list: D005290:Ferric Compounds; D011136:Polysorbates; C001215:ferrite; D004998:Ethiodized Oil
keywords: Computed tomography; Lipiodol; embolisation therapy; hyperthermia; image-guided delivery; magnetic nanoparticles; magnetic resonance imaging