title: Targeting the insulin growth factor-1 receptor with fluorescent antibodies enables high resolution imaging of human pancreatic cancer in orthotopic mouse models.
abstract: 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.
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA, USA.|AntiCancer, Inc., San Diego, CA, USA.|Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jeong Youp
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA, USA.|AntiCancer, Inc., San Diego, CA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA, USA.|Surgical Service, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019085:Fluorescent Antibody Technique, Direct / Q000379:methods*; D005456:Fluorescent Dyes / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000276:immunology*
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D017526:Receptor, IGF Type 1
keywords: fluorescent antibody; imaging; insulin-like growth factor-1 receptor (IGF-1R); orthotopic nude mice; pancreatic cancer