RECEPTOR TARGETING

Application Overview

Cell surface receptors can be targeted for in vivo imaging by injection of agents that bind specifically to the receptor.

Tumor cells often over-express certain cell surface receptors (for example, EGFR or integrins).
Fluorescently-labeled molecules (such as ligands, antibodies, or drugs) that specifically bind these receptors can be used to visualize tumors inside the living animal.
Epidermal growth factor receptor (EGFR), overexpressed on the cell surface of many cancer cells types¹, can be targeted with a fluorescently labeled IRDye EGF agent for longitudinal studies of tumor progression².
Tumors over-expressing integrin receptors can be targeted with IRDye^® 800CW RGD Optical Probe^3,4.

Near-infrared dyes, such as IRDye fluorophores, and carefully optimized hardware are critical for high-performance optical imaging.

Near-infrared fluorophores exploit the spectral region where light absorption and scatter properties of tissue are most advantageous⁵. This enhances penetration depth (access of excitation light to the fluorophore) and escape of emitted fluorescence from the animal to reach the detector.
Laser illumination delivers very intense excitation light of the correct wavelength, generating the brightest possible signal from the fluorescent agent.
Intrinsic autofluorescence from animal tissue can mask the signal from optical probes. In the NIR spectral region, autofluorescence is dramatically lowered^6,7.

¹ Hong, W. and A. Ullrich. Oncology Biotherapeutics. 1(1): 5 (2000)

² Kovar, J et al. Am J Pathol. 169(4):1415-26 (2006)

³ Kovar, J et al. Poster presentation, AACR Annual Meeting (2009)

⁴ Chen, K et al. Mol Imaging. 8(2):65-73 (2009)

⁵ Hawrysz, DJ and Sevick-Muraca, EM. Neoplasia. 2(5):388–417 (2000)

⁶ Frangioni, JV. Curr Opin Chem Biol. 7(5):626-34 (2003)

⁷ Adams, KE, et al. J Biomed Opt. 12(2):024017 (2007)

Figure 1. IRDye 800CW EGF imaged 96 h post injection. Orange ovals pinpoint region of orthotopic implanted prostate tumor. Images were captured with the Pearl Imager with the pseudo-color representing the 800 nm channel.

Figure 2. Nude mouse bearing subcutaneous tumors, U87 (left hip) and A431(right hip), was imaged 24 hours post intravenous injection of IRDye 800CW RGD (1 nmole). Image was captured on the Pearl Imager; 800nm signal is presented in pseudo-color overlaid on a white light image of the mouse.

Technical Resources

Why Image in the NIR?

“Advances in In Vivo Imaging: Near-Infrared Optical Imaging of Mice”
Jeff Harford, LI-COR
“Instrumentation and Imaging Considerations”
Eva Sevick-Muraca, Baylor College of Medicine
“In vivo imaging of prostate cancer using an IRDye 800CW EGF Optical Probe"
Melanie Simpson, University of Nebraska – Lincoln
“Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer”
Eva Sevick-Muraca and Shi Ke, Baylor College of Medicine

Development of imaging agents

“Systematic Evaluation and Use of Targeted IRDye labeled Optical Contrast Agents”
Mike Olive, LI-COR
“Systematic Evaluation of Targeted IRDye Labeled Optical Imaging Agents”
Joy Kovar, LI-CORs
“Near Infrared Fluorescent Approaches to Cell-Based Assays and Small Animal Imaging”
Amy Geschwender, LI-COR

Targeted Imaging

"Illuminating Prostate Cancer Progression"
Melanie Simpson, University of Nebraska - Eppley Cancer Center
See Small Animal Imaging application page for more related webinars.