Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors

Sci Rep. 2019 Aug 7;9(1):11476. doi: 10.1038/s41598-019-47808-y.


Osteosarcoma (OS) represents 3.4% of all childhood cancers with overall survival of 70% not improving in 30 years. The consistent surface overexpression of insulin-like growth factor-2 receptor (IGF2R) has been reported in commercial and patient-derived xenograft (PDX) OS cell lines. We aimed to assess efficacy and safety of treating PDX and commercial OS tumors in mice with radiolabeled antibody to IGF2R and to investigate IGF2R expression on canine OS tumors. IGF2R expression on human commercial lines 143B and SaOS2 and PDX lines OS-17, OS-33 and OS-31 was evaluated by FACS. The biodistribution and microSPECT/CT imaging with 111Indium-2G11 mAb was performed in 143B and OS-17 tumor-bearing SCID mice and followed by radioimmunotherapy (RIT) with 177Lutetium-2G11 and safety evaluation. IGF2R expression in randomly selected canine OS tumors was measured by immunohistochemistry. All OS cell lines expressed IGF2R. Biodistribution and microSPECT/CT revealed selective uptake of 2G11 mAb in 143B and OS-17 xenografts. RIT significantly slowed down the growth of OS-17 and 143B tumors without local and systemic toxicity. Canine OS tumors expressed IGF2R. This study demonstrates the feasibility of targeting IGF2R on OS in PDX and spontaneous canine tumors and sets the stage for further development of RIT of OS using comparative oncology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects
  • Bone and Bones / pathology
  • Bone and Bones / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Dog Diseases / diagnostic imaging
  • Dog Diseases / pathology
  • Dog Diseases / therapy*
  • Dogs
  • Feasibility Studies
  • Female
  • Humans
  • Immunoconjugates / administration & dosage*
  • Mice
  • Osteosarcoma / diagnostic imaging
  • Osteosarcoma / pathology
  • Osteosarcoma / therapy*
  • Radioimmunotherapy / methods*
  • Receptor, IGF Type 2 / antagonists & inhibitors
  • Receptor, IGF Type 2 / metabolism*
  • Single Photon Emission Computed Tomography Computed Tomography
  • X-Ray Microtomography
  • Xenograft Model Antitumor Assays


  • IGF2R protein, human
  • Immunoconjugates
  • Receptor, IGF Type 2