Multiplexing drug-target engagement and metabolic imaging in HER2-positive tumor xenograft models

Macroscopic fluorescence lifetime FRET imaging (MFLI-FRET) presents a much-needed analytical tool to non-invasively quantify drug-receptor engagement in tumors and other organs in preclinical studies. We demonstrate the specificity and sensitivity of MFLI-FRET for direct and robust measurement of trastuzumab-HER2 target engagement in various types of breast and ovarian cancer tumor xenograft models. Simultaneous metabolic imaging with IRDye 800 CW 2-DG reveals that intracellular delivery of drug is associated with 2-DG lifetime and likely reflects tumors’ microenvironment and perfusion state.