Recent advances in optical cancer imaging of EGF receptors

Abstract

Epidermal growth factor (EGF) receptors are commonly expressed on the cell membrane of cancer cells and activity of these receptors results in accelerated cell growth and carcinogenesis. A variety of targeted molecules have been developed to block ligand binding and/or inhibit the function of these receptor tyrosine kinases, and several have proven therapeutic benefits. Along with the advent of new therapeutic agents comes a need for non-invasive tools to diagnose, characterize, and monitor tumor responsiveness to therapy. Imaging EGF receptors with radionuclides has been performed for decades. However, recently this area has advanced considerably with the development of EGF receptor-targeted optical imaging probes. Herein, we review recent advances in molecular imaging of the EGF receptor family, focusing specifically on optical imaging. Such agents provide the opportunity for earlier diagnosis, improved tumor characterization, and the ability to measure and monitor tumor responsiveness to anti-EGF receptor treatment strategies.

Fig. (1).

A schema for structures of HER1 and HER2 receptors with references of each receptor over-expressing cancers.

Fig. (2).

A) Representative coronal section of ¹⁸F-Affibody_HER2 uptake. The HER2-positive lung metastases are visualized 1 h post tracer injection. B) Ex vivo bioluminescence image of the same mouse shows photon signals consistent with PET signals shown in A.

Fig. (3).

Accumulation of DyLight750-Affibody_HER2 in xenografts was well correlated with HER2 expression levels. (Figures courtesy of Dr. Rafal Zielinski.)

Fig. (4).

Two-color HER1 and HER2 image is shown. A cocktail injection of Cy5.5-labeled panitumumab (anti-HER1; shown in red) and Cy7-labeled trastuzumab (anti-HER2; shown in green) clearly depicts MDA-MB-468 breast cancer (HER1-positive) in the right breast and SKOV3 ovarian cancer (HER2-positive) in the navel in the tumor-bearing mice in distinct colors.

Fig. (5).

Activatable ICG-labeling of panitumumab (anti-HER1) and trastuzumab (anti-HER2) clearly depicted respective antigen-positive tumors in tumors-bearing mice.