Targeting the insulin growth factor-1 receptor with fluorescent antibodies enables high resolution imaging of human pancreatic cancer in orthotopic mouse models
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Jeong Youp Park1,2,3, Jin Young Lee3, Yong Zhang2, Robert M. Hoffman1,2, Michael Bouvet1,4
1Department of Surgery, University of California San Diego, San Diego, CA, USA
2AntiCancer, Inc., San Diego, CA, USA
3Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
4Surgical Service, VA San Diego Healthcare System, San Diego, CA, USA
Michael Bouvet, email: firstname.lastname@example.org
Keywords: insulin-like growth factor-1 receptor (IGF-1R), fluorescent antibody, orthotopic nude mice, imaging, pancreatic cancer
Received: December 03, 2015 Accepted: February 11, 2016 Published: February 22, 2016
The goal of the present study was to determine whether insulin-like growth factor-1 receptor (IGF-1R) antibodies, conjugated with bright fluorophores, could enable visualization of pancreatic cancer in orthotopic nude mouse models. IGF-1R antibody (clone 24-31) was conjugated with 550 nm or 650 nm fluorophores. Western blotting confirmed the expression of IGF-1R in Panc-1, BxPC3, and MIAPaCa-2 human pancreatic cancer cell lines. Labeling with fluorophore-conjugated IGF-1R antibody demonstrated fluorescent foci on the membrane of the pancreatic cancer cells. Subcutaneous Panc-1, BxPC-3, and MIA PaCa-2 tumors became fluorescent after intravenous administration of fluorescent IGF-1R antibodies. Orthotopically-transplanted BxPC-3 tumors became fluorescent with the conjugated IGF-1R antibodies, and were easily visible with intravital imaging. Gross and microscopic ex vivo imaging of resected pancreatic tumor and normal pancreas confirmed that fluorescence indeed came from the membrane of cancer cells, and it was stronger from the tumor than the normal tissue. The present study demonstrates that fluorophore-conjugated IGF-1R antibodies can visualize pancreatic cancer and it can be used with various imaging devices such as endoscopy and laparoscopy for diagnosis and fluorescence-guided surgery.
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