Translational Research

Publications: Tumor Imaging with IRDye 800CW - EGF

(Epidermal Growth Factor Receptor)

Many types of cancer cells express abnormally high levels of epidermal growth factor receptor (EGFR) on their surface (Table 1). This potential cancer biomarker binds EGF which has been shown to be an effective imaging agent.

IRDye 800CW has been used in a number of studies to label agents for imaging various types of tumors. Targeting agents include: EGF, EGFR antibody and EGFR affibody.

EGF

Apoptosis-inducing effect of erlotinib is potentiated by 3,3'-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer
Shadan Ali, Sanjeev Banerjee, Aamir Ahmad, Bassel F. El-Rayes, Philip A. Philip, and Fazlul H. Sarkar Mol. Cancer Ther., Jun 2008; 7: 1708 - 1719.

Hyaluronidase Expression Induces Prostate Tumor Metastasis in an Orthotopic Mouse Model
Joy L. Kovar, Mark A. Johnson, William M. Volcheck, Jiyan Chen, and Melanie A. Simpson
Am. J. Pathol., Oct 2006; 169: 1415 - 1426.

EGF-IRDye 800CW: in vitro and in vivo characterization as a biomarker for optical fluorescent imaging of tumor growth kinetics.
Joy L. Kovar, Mark A. Johnson, William M. Volcheck, Jiyan Chen, and Melanie A. Simpson
Poster presentation, SMI Annual Meeting (2005)

Spontaneous Metastasis of Prostate Cancer Is Promoted by Excess Hyaluronan Synthesis and Processing
Alamelu G. Bharadwaj, Joy L. Kovar, Eileen Loughman, Christian Elowsky, Gregory G. Oakley, and Melanie A. Simpson
Am. J. Pathol., Mar 2009; 174: 1027 - 1036.

Molecular Imaging of Therapeutic Response to Epidermal Growth Factor Receptor Blockade in Colorectal Cancer
H. Charles Manning, Nipun B. Merchant, A. Coe Foutch, John M. Virostko, Shelby K. Wyatt, Chirayu Shah, Eliot T. McKinley, Jingping Xie, Nathan J. Mutic, M. Kay Washington, Bonnie LaFleur, Mohammed Noor Tantawy, Todd E. Peterson, M. Sib Ansari, Ronald M. Baldwin, Mace L. Rothenberg, Darryl J. Bornhop, John C. Gore, and Robert J. Coffey
Clin. Cancer Res., Nov 2008; 14: 7413 - 7422.

Antitumor Activity of Gemcitabine and Oxaliplatin Is Augmented by Thymoquinone in Pancreatic Cancer
Sanjeev Banerjee, Ahmed O. Kaseb, Zhiwei Wang, Deujan Kong, Mussop Mohammad, Subhash Padhye, Fazlul H. Sarkar, and Ramzi M. Mohammad
Cancer Res., Jul 2009; 69: 5575 - 5583.

EGFR Antibody

Multifunctional and multiplexed nanoparticles for molecular imaging and treatment of breast cancer.
L Yang, H Sajja, Z Cao, AY Wang, MQ Smith, L Bender, H Mao, S Nie, and WC Wood
Cancer Res., Jan 2009; 69: 6003.

Dual-labeled trastuzumab-based imaging agent for the detection of human epidermal growth factor receptor 2 overexpression in breast cancer.
Sampath L, Kwon S, Ke S, Wang W, Schiff R, Mawad ME, Sevick-Muraca EM.
J Nucl Med. 2007 Sep;48(9):1501-10.

In Vivo Imaging of Xenograft Tumors Using an Epidermal Growth Factor Receptor–Specific Affibody Molecule Labeled with a Near-infrared Fluorophore1
Haibiao Gong, Joy Kovar, Garrick Little, Huaxian Chen and David Michael Olive.
Neoplasia 12: 139 (2010)

Gong et al. labeled an EGFR-specific Affibody molecule (Eaff) with IRDye800CW maleimide and tests showed that Eaff800 was bound and taken up specifically by EGFR-overexpressing A431 cells. When Eaff800 was intravenously injected into nude mice bearing A431 xenograft tumors, the tumor could be identified 1 hour after injection and it became most prominent after 1 day. In combination with a human EGFR type 2 (HER2)–specific probe Haff682, Eaff800 could be used to distinguish between EGFR- and HER2-overexpressing tumors.

Trastuzumab

Dual-Labeled Trastuzumab-Based Imaging Agent for the Detection of Human Epidermal Growth Factor Receptor 2 Overexpression in Breast Cancer
Lakshmi Sampath, Sunkuk Kwon, Shi Ke, Wei Wang, Rachel Schiff, Michel E. Mawad, and Eva M. Sevick-Muraca
Journal of Nuclear Medicine 48: 1501 (2007)

Sampath et al. exploited the extracellular binding property of trastuzumab, a clinically therapeutic monoclonal antibody to HER2, to design a diagnostic imaging agent, (111In-DTPA) n-trastuzumab-(IRDye 800CW), that is dual labeled with 111In, a g-emitter, and a near-infrared (NIR) fluorescent dye, IRDye 800CW, to detect HER2 overexpression in breast cancer cells. They demonstrated the molecular specificity of the dual-labeled imaging agent targeting HER2 in cell lines as well as in a standard subcutaneous animal model of human breast cancer. In vitro and in vivo results confirmed the molecular specificity of targeting.They showed the ability to deliver the antibody-based agent into the lymphatics through intradermal injection as well as clearance from the regional lymphatic space after 24 h. It was concluded the dual-labeled (111In-DTPA)n-trastuzumab-(IRDye800) may be an effective diagnostic biomarker capable of tracking HER2 overexpression in breast cancer patients.