Targeting the insulin growth factor-1 receptor with fluorescent antibodies enables high resolution imaging of human pancreatic cancer in orthotopic mouse models.

Jeong Youp Park,Michael Bouvet,Jin Young Lee,Yong Zhang,Robert M Hoffman

doi:10.18632/oncotarget.7576

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.

Highlights

For pancreatic cancer, CA19-9 is the only biomarker being used in the clinic despite many needs for others [1,2,3]
We previously demonstrated that CEA, CA19-9, and MUC1 could be targeted in pancreatic cancer with specific fluorescent antibodies, enabling imaging in orthotopic mouse models [7,8,9]
After incubation with the fluorophoreconjugated insulin-like growth factor-1 receptor (IGF-1R) antibody, without permeation, multiple fluorescent foci were visualized on the membrane of Panc1 and BxPC-3 cells under fluorescence microscopy (Figure 1B) confirming the expression of IGF-1R on cancer cells

Summary

Introduction

CA19-9 is the only biomarker being used in the clinic despite many needs for others [1,2,3]. We previously demonstrated that CEA, CA19-9, and MUC1 could be targeted in pancreatic cancer with specific fluorescent antibodies, enabling imaging in orthotopic mouse models [7,8,9]. Type I insulin-like growth factor receptor (IGF-1R) is a potential diagnostic and therapeutic biomarker of several cancers [10]. It is a transmembrane tyrosine kinase receptor comprising two α and two β chains. A few studies have shown fluorescence imaging using IGF-1R targeting on tumors is possible, and its potential clinical usefulness has been discussed [16]. We demonstrate that fluorescent anti-IGF-1R antibodies target pancreatic cancer in orthotopic mouse models enabling non-invasive imaging and high resolution intra-vital imaging of the tumor

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Conclusion