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

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...

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Main Authors: England,Christopher G, Kamkaew,Anyanee, IM,Hyung-Jun, Valdovinos,Hector F, Sun,Haiyan, Hernandez,Reinier, Cho,Steve Y, Dunphy,Edward J, Lee,Dong Soo, Barnhart,Todd E, Cai,Weibo
Format: Report
Language:English
Subjects:
(pet)Positron emission tomography
89zr(Zirconium-89)
antibodies
cancer research
DIAGNOSTIC IMAGING
growth factors
igf-1r(Insulin-like growth factor-1 receptor)
imaging techniques
in vivo analysis
Molecular imaging
neoplasms
PANCREATIC DISEASES
Positron emission tomography
therapeutics
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Summary: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 radio labeling 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 ofIGF-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 post injection, 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 post injection; 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. Molecular Pharmaceutics , 13, 6, 01 Jan 0001, 01 Jan 0001, Open Access: Publishers Version. May be placed on public websites; ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.