Ex vivo mesoscopic assessment of drug delivery and target engagement via lifetime FRET

Abstract

Time-domain mesoscopic fluorescence molecular tomography (TD-MFMT) provides a unique window for non-invasively monitoring drug delivery efficacy parameters in targeted anticancer research, such as drug-receptor engagement and intra-tumoral heterogeneity. We investigate the potential of TD-MFMT for ex vivo assessment of Trastuzumab-HER2 target engagement and drug distribution in two types of breast and ovarian cancer tumor xenograft models (AU565 and SK-OV-3) via lifetime FRET technique. FRET fraction level and fluorescence drug distribution results reveal that drug accumulation within tumors cannot be automatically associated with targeted cellular drug delivery.