ImmunoPET Imaging of Insulin-Like Growth Factor 1 Receptor in a Subcutaneous Mouse Model of Pancreatic Cancer

Christopher G. England, Anyanee Kamkaew, Hyung Jun Im, Hector F. Valdovinos, Haiyan Sun, Reinier Hernandez, Steve Y. Cho, Edward J. Dunphy, Dong Soo Lee, Todd E. Barnhart, Weibo Cai

Research output: Contribution to journalArticle

Abstract

The role of insulin-like growth factor-1 receptor (IGF-1R) in cancer tumorigenesis was established decades ago, yet there are limited studies evaluating the imaging and therapeutic properties of anti-IGF-1R antibodies. Noninvasive imaging of IGF-1R may allow for optimized patient stratification and monitoring of therapeutic response in patients. Herein, this study reports the development of a Zirconium-89 (89Zr)-labeled anti-IGF-1R antibody (89Zr-Df-1A2G11) for PET imaging of pancreatic cancer. Successful chelation and radiolabeling of the antibody resulted in a highly stable construct that could be used for imaging IGF-1R expressing tumors in vivo. Western blot and flow cytometry studies showed that MIA PaCa-2, BxPC-3, and AsPC-1 pancreatic cancer cell lines expressed high, moderate, and low levels of IGF-1R, respectively. These three pancreatic cancer cell lines were subcutaneously implanted into mice. By employing the PET imaging technique, the tumor accumulation of 89Zr-Df-1A2G11 was found to be dependent on the level of IGF-1R expression. Tumor accumulation of 89Zr-Df-1A2G11 was 8.24 ± 0.51, 5.80 ± 0.54, and 4.30 ± 0.42 percentage of the injected dose (%ID/g) in MIA PaCa-2, BxPC-3, and AsPC-1-derived tumor models at 120 h postinjection, respectively (n = 4). Biodistribution studies and ex vivo immunohistochemistry confirmed these findings. In addition, 89Zr-labeled nonspecific human IgG (89Zr-Df-IgG) displayed minimal uptake in IGF-1R positive MIA PaCa-2 tumor xenografts (3.63 ± 0.95%ID/g at 120 h postinjection; n = 4), demonstrating that 89Zr-Df-1A2G11 accumulation was highly specific. This study provides initial evidence that our 89Zr-labeled IGF-1R-targeted antibody may be employed for imaging a wide range of malignancies. Antibodies may be tracked in vivo for several days to weeks with 89Zr, which may enhance image contrast due to decreased background signal. In addition, the principles outlined in this study can be employed for identifying patients that may benefit from anti-IGF-1R therapy.

Original languageEnglish (US)
Pages (from-to)1958-1966
Number of pages9
JournalMolecular Pharmaceutics
Volume13
Issue number6
DOIs
StatePublished - Jun 6 2016

Keywords

  • Insulin-like growth factor-1 receptor (IGF-1R)
  • Molecular imaging
  • Positron emission tomography (PET)
  • Zirconium-89 (Zr)

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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  • Cite this

    England, C. G., Kamkaew, A., Im, H. J., Valdovinos, H. F., Sun, H., Hernandez, R., Cho, S. Y., Dunphy, E. J., Lee, D. S., Barnhart, T. E., & Cai, W. (2016). ImmunoPET Imaging of Insulin-Like Growth Factor 1 Receptor in a Subcutaneous Mouse Model of Pancreatic Cancer. Molecular Pharmaceutics, 13(6), 1958-1966. https://doi.org/10.1021/acs.molpharmaceut.6b00132