title: Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R).
abstract: BACKGROUND
  Osteosarcoma overall survival has plateaued around 70%, without meaningful improvements in over 30years. Outcomes for patients with overt metastatic disease at presentation or who relapse are dismal. In this study we investigated a novel osteosarcoma therapy utilizing radioimmunotherapy (RIT) targeted to IGF2R, which is widely expressed in OS.
  
  
  METHODS
  Binding efficiency of the Rhenium-188(188Re)-labeled IGF2R-specific monoclonal antibody (mAb) to IGF2R on OS17 OS cells was assessed with Scatchard plot analysis. Biodistribution studies were performed in heterotopic murine osteosarcoma xenografts. Tumor growth was compared over a 24-day period post-treatment between mice randomized to receive188Re-labeled IGF2R-specific murine mAb MEM-238 (188Re-MEM-238) or one of three controls:188Re-labeled isotype control mAb, unlabeled MEM-238, or no treatment.
  
  
  RESULTS
  Results demonstrate that the radioimmunoconjugate had a high binding constant to IGF2R. Both188Re-MEM-238 and the isotype control had similar initial distribution in normal tissue. After 48h188Re-MEM-238 exhibited a 1.8 fold selective uptake within tumor compared to the isotype control (p=0.057). Over 24days, the tumor growth ratio was suppressed in animals treated with RIT compared to unlabeled and untreated controls (p=0.005) as demonstrated by a 38% reduction of IGF2R expressing osteosarcoma cells in the RIT group (p=0.002).
  
  
  CONCLUSIONS
  In conclusion, given the lack of new effective therapies in osteosarcoma, additional investigation into this target is warranted.
  
  
  CONCLUSIONS
  High expression of IGF2R on osteosarcoma tumors, paired with the specificity and in vivo anti-cancer activity of188Re-labeled IGF2R-specific mAb suggests that IGF2R may represent a novel therapeutic target in the treatment of osteosarcoma.
  
  
  CONCLUSIONS
  This targeted approach offers the benefits of being independent of a specific pathway, a resistance mechanism, and/or an inherent biologic tumor trait and therefore is relevant to all OS tumors that express IGF2R.
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: dgeller@montefiore.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Geller
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Morris
authors.affiliation: Department of Radiology, Nuclear Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Revskaya
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: Mani
authors.initials: M
authors.lastname: Kahn
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: Wendong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: Sajida
authors.initials: S
authors.lastname: Piperdi
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Pratistha
authors.initials: P
authors.lastname: Koirala
authors.affiliation: Analytical Imaging Facility, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Hillary
authors.initials: H
authors.lastname: Guzik
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Hall
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Bang
authors.initials: B
authors.lastname: Hoang
authors.affiliation: Department of Orthopaedic Surgery, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gill
authors.affiliation: Department of Pediatrics, Montefiore Medical Center and The Children's Hospital at Montefiore, Bronx, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA; Department of Radiology, Nuclear Medicine, Montefiore Medical Center, Bronx, NY, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D021381:Protein Transport; D016499:Radioimmunotherapy / Q000379:methods*; D017527:Receptor, IGF Type 2 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017527:Receptor, IGF Type 2
keywords: Insulin-like growth factor-2 receptor (IGF2R); OS; Radioimmunotherapy; Rhenium-188