title: ImmunoPET Imaging of Insulin-Like Growth Factor 1 Receptor in a Subcutaneous Mouse Model of Pancreatic Cancer.
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 ((89)Zr)-labeled anti-IGF-1R antibody ((89)Zr-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 (89)Zr-Df-1A2G11 was found to be dependent on the level of IGF-1R expression. Tumor accumulation of (89)Zr-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, (89)Zr-labeled nonspecific human IgG ((89)Zr-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 (89)Zr-Df-1A2G11 accumulation was highly specific. This study provides initial evidence that our (89)Zr-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 (89)Zr, 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.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: England
authors.forename: Anyanee
authors.initials: A
authors.lastname: Kamkaew
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Department of Nuclear Medicine, Seoul National University , Seoul 110-744, Korea.
authors.forename: Hyung-Jun
authors.initials: HJ
authors.lastname: Im
authors.forename: Hector F
authors.initials: HF
authors.lastname: Valdovinos
authors.forename: Haiyan
authors.initials: H
authors.lastname: Sun
authors.forename: Reinier
authors.initials: R
authors.lastname: Hernandez
authors.forename: Steve Y
authors.initials: SY
authors.lastname: Cho
authors.affiliation: NeoClone Biotechnologies International , Madison, Wisconsin 53713, United States.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dunphy
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Department of Nuclear Medicine, Seoul National University , Seoul 110-744, Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011868:Radioisotopes / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D014018:Tissue Distribution / Q000502:physiology; D015040:Zirconium / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D015040:Zirconium; D017526:Receptor, IGF Type 1
keywords: Insulin-like growth factor-1 receptor (IGF-1R); Molecular imaging; Positron emission tomography (PET); Zirconium-89 (89Zr)