Principal Investigator Ralph Weissleder
By harnessing a recently developed bioorthogonal in vivo detection (BIND) chemistry, which involves the highly specific and fast reaction between strained trans-cyclooctene and tetrazine derivatized imaging reporters, we are developing cell permeable small molecule affinity ligand-based imaging probes as companions to therapeutic drugs. In parallel we are developing BODIPY derived drug conjugates which are both fluorescent and can be labeled with 18F. Both approaches are used to modify small molecule drugs to image EGFR, VEGFR, HER2, C-MET, MEK, PI3K/mTOR, PARP1, PLK1, AKA, BCL-2, among others. We typically first develop and test library of compounds and validate key hits by imaging by intravital microscopy. We also focus on the protein-wide identification and validation of binding partners of lead compounds, for which we will use in vitro and in vivo proteomic approaches. These experiments are critical since a comprehensive understanding of the interacting proteins and their associated protein complexes is important for the development of imaging agents and the interpretation of imaging studies. Finally, we explore the translational potential of these companion imaging drugs in therapeutic trials.