There is a need to develop more sensitive, specific and robust strategies capable of imaging and quantitating therapeutic targets In cancers in vivo. To date, many biological targets and processes remain largely unobserved due to a) lack of affinity ligands, b) mismatches between target abundance and the amount of imaging agent required for target visualization, c) delivery barriers, d) unfavorable pharmacokinetics, e) high background signals, f) the unavailability of appropriate affinity ligands, and/or g) the sheer numbers of targets. The goal of this project is to use a recently developed bioorthogonal platform technology (known as BIND) for the rapid development of intracellular imaging agents such as polo-lil The specific aims are: 1) to develop a library of PLK-1 and PARP1-targeted BIND agents and characterize them biochemically, using live cell imaging and intravital microscopy;2) to perform target-identification and network analysis using in vivo proteomics (SILAC);and 3) to explore the translational potential using ^^F-labeled agents in gemcitabine and PLKHnhibitor/PARPinhibitor treated mice.

Public Health Relevance

The proposed work will likely lead to more sensitive, rapid and robust generic methods for imaging and quantifying therapeutic targets in cancer. Such technologies will enable physicians to stratify patients into appropriate treatment groups and to detect emerging drug resistance.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Special Emphasis Panel (ZCA1-SRLB-9)
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Massachusetts General Hospital
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