The discovery and implementation of molecularly targeted imaging modalities has progressed considerably in recent years. Our interest centers on the design and synthesis of near-IR fluorophores, which are employed extensively in microscopy and in vivo optical imaging. One such agent, indocyanine green, is FDA approved and currently involved in over 100 active clinical trials, including over 20 for cancer diagnosis. Despite a central role in modern biology and medicine, the compounds employed in near-IR fluorescence techniques have changed little in recent decades. Using molecular design concepts borrowed from related fields (e.g. medicinal chemistry and natural product synthesis), we seek to develop new agents with improved utility for cancer-related imaging. Specifically, we are developing near-IR fluorophores, especially in the cyanine class, with improved fluorescence properties and chemical stability. At this stage, the focus of the lab centers on the development of concise, modular synthetic approaches to target molecules. We have identified a new target-fluorophore linking strategy that imparts dramatically improved stability. The compounds we prepare will be applied in a variety of contexts to enable improved readout of biological processes, particularly in the area of cancer diagnosis. We have developed key collaborations (Mitchell and Krishna) to enable our small molecule synthesis-oriented group to evaluate our agents in in vivo settings.
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