Biochemistry, Department of
Document Type
Article
Date of this Version
8-1-2007
Abstract
In the past decade, our increased elucidation of the molecular basis of cancer has led to the development of novel targeted strategies for specific inhibition of cancer signaling pathways that control growth, proliferation, apoptosis, and angiogenesis. Several monoclonal-antibody-based therapeutics and small-molecule drugs have received clearance for use as human therapeutics [1]. However, among these successes are many candidate drugs that have failed in clinical trials despite promising preclinical results [2]. The development of targeted therapeutics is expensive and time consuming. In their Critical Path Initiative, the United States Food and Drug Administration emphasized the need for more effective tools to facilitate the rapid development of improved cancer therapeutics. One such tool is the use of targeted molecular optical imaging probes or contrast agents to visualize the underlying processes in cancer. Optical imaging, also known as molecular imaging, is a rapidly developing field of research aimed at noninvasively interrogating animals for disease progression, evaluating the effects of a drug, assessing the pharmacokinetic behavior of a drug, or identifying molecular biomarkers of disease. A prerequisite of molecular imaging is the development of specific, targeted imaging contrast agents to assess these biological processes. Several optical aids have shown great utility in animal studies, including bioluminescence, fluorescent proteins, and fluorochrome-labeled agents. However, only the latter have the advantage of being potentially relevant to human clinical applications. The complexity of developing robust fluorochrome-labeled optical agents is often underestimated. Many studies describe the use of these agents, but guidelines for their development and testing are not readily available. The purpose of this review is to outline some of the considerations for developing and using fluorochrome-labeled optical contrast agents in animals. For simplicity, we have focused on the use of organic fluorochromes as labeling agents. These types of probes are generally the most straightforward to develop and have the greatest potential for translation to human clinical use. Nanoparticles such as quantum dots, while useful for some animal studies, are hampered by clearance issues and toxicity and will not be specifically discussed. However, the principles described here are generally applicable to any fluorescent optical imaging agent.
Comments
Published in Analytical Biochemistry 367:1 (August 1, 2007), pp. 1-12. Copyright © 2007 Elsevier Inc. Used by permission. www.sciencedirect.com/science/journal/00032697