Since 2004 the U.S. Food and Drug Administration has approved three new-generation anticancer therapies that target epidermal growth factor receptor (EGFR), a protein that is greatly overexpressed on certain types of tumors, including some forms of colorectal and lung cancer.
For patients with EGFR-positive tumors, these drugs can be lifesavers, but at present, there is no good way to predict who will respond to anti-EGFR therapy. That may change, though, thanks to the development of two quantum dot-based systems that can image EGFR expression in living animals.
Reporting its work in the journal Clinical Cancer Research, a team of investigators at the M.D. Anderson Cancer Center, led by Sunil Krishnan, M.D., and Juri Gelovani M.D., Ph.D., describes its design of a near-infrared quantum dot linked to epidermal growth factor and used to image tumors that overexpress EGFR in a mouse model of human colon cancer. Binding assays showed that this construct was capable of recognizing and binding to EGFR with only a slight reduction in affinity compared with native epidermal growth factor. However, activity assays showed that the targeted quantum dot did not activate EGFR, which could cause complications for a potential imaging agent by triggering unwanted tumor cell growth.
Using a mouse model of human colon cancer, the investigators then assessed this quantum dot’s utility as an in vivo imaging agent. After injecting tumor-bearing animals with the quantum dots, the investigators tracked the distribution of these probes using a commercial fluorescence imaging system. As a control, the researchers injected some animals with an untargeted quantum dot. Within 3 minutes of injection, the researchers were able to observe the quantum dots distributing throughout the body, but over the next hour, only the targeted quantum dots accumulated within tumors. By 24 hours after injection, fluorescence levels in animals for both targeted and untargeted quantum dots had dropped to near zero.
Moungi Bawendi, Ph.D., and colleagues at the Massachusetts Institute of Technology have also developed an EGFR-targeted quantum dot capable of imaging live cells, although his group’s efforts to date have focused on working out new chemical methods for preparing compact biocompatible quantum dots. These methods, which should also simplify the development of a wide range of targeted quantum dot imaging probes, appear in a paper published in the Journal of the American Chemical Society.
The work conducted by Dr. Krishnan, Dr. Gelovani, and their collaborators is detailed in the paper “Imaging epidermal growth factor receptor expression in vivo: pharmacokinetic and biodistribution characterization of a bioconjugated quantum dot nanoprobe.” An abstract of this paper is available through PubMed.
Dr. Bawendi and group’s work is described in the paper “Compact biocompatible quantum dots functionalized for cellular imaging.” Dr. Bawendi is a member of the MIT-Harvard Center of Cancer Nanotechnology Excellence, and this work was funded in part by the NCI’s Alliance for Nanotechnology in Cancer. An abstract of this paper is available through PubMed.