title: High specificity targeting and detection of human neuroblastoma using multifunctional anti-GD2 iron-oxide nanoparticles.
abstract: OBJECTIVE
  To develop biocompatible, tumor-specific multifunctional iron-oxide nanoconstructs targeting neuroblastoma, an aggressive pediatric malignancy.
  
  
  METHODS
  Clinical-grade humanized monoclonal antibody (hu14.18K322A), designed to target GD2 antigen on neuroblastoma with reduced nonspecific immune interactions, was conjugated to hydroxyethyl starch-coated iron-oxide nanoparticles. Targeting capability in vitro and in vivo was assessed by immunofluorescence, electron microscopy, analytical spectrophotometry, histochemistry and magnetic resonance R2* relaxometry.
  
  
  RESULTS
  The biocompatible nanoconstructs demonstrated high tumor specificity in vitro and in vivo, and low background uptake in a mouse flank xenograft model. Specific accumulation in tumors enabled particle visualization and quantification by magnetic resonance R2* mapping.
  
  
  CONCLUSIONS
  Our findings support the further development toward clinical application of this anti-GD2 iron-oxide nanoconstruct as diagnostic and therapeutic scaffold for neuroblastoma and potentially other GD2-positive malignancies.
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology, Oncology & Bone Marrow Transplant, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Baiu
authors.affiliation: Department of Radiology, Medical Physics, Biomedical Engineering, Medicine & Emergency Medicine, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Artz
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology, Oncology & Bone Marrow Transplant, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Meghan R
authors.initials: MR
authors.lastname: McElreath
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology, Oncology & Bone Marrow Transplant, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Menapace
authors.affiliation: Department of Radiology, Medical Physics, Biomedical Engineering, Medicine & Emergency Medicine, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Hernando
authors.affiliation: Department of Radiology, Medical Physics, Biomedical Engineering, Medicine & Emergency Medicine, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Reeder
authors.affiliation: Micromod Partikeltechnologie GmbH, 18119 Rostock, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Grüttner
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology, Oncology & Bone Marrow Transplant, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Otto
keywords: MRI; anti-GD2; cancer; iron-oxide nanoparticle; neuroblastoma; pediatric; tumor targeted