Optical imaging of zebrafish xenograft tumors for a high throughput drugs screen

Breast cancer is the second most common cancer among women in the United States. Heterogeneity in breast cancer treatment response across patients indicates that patient-specific treatment screens will reduce under-treatment of aggressive and recurrent cancers, while also sparing patients with non-aggressive disease toxicities due to over-treatment. Xenografts grown from patient-specific tissue in zebrafish present a novel platform for a medium to high-throughput anti-cancer drug screen to individualize patient therapy. The goal of this project is to develop an optical imaging anti-cancer drug screen to evaluate patient-specific zebrafish tumors. Trastuzumab (anti-HER2 antibody) responsive and resistant breast cancer cells were injected into 48 hour-post-fertilization zebrafish embryos. Tumors were established for 24 hours and then fish were treated with a panel of breast cancer drugs and drug combinations. Autofluorescence lifetime images with single-cell resolution of the fish tumors were acquired at 24, 48, and 72 hours of drug treatment. Wide-field mCherry fluorescence and brightfield images with fish-level resolution were acquired prior to treatment (t=0 hour) and at 72 hours of drug treatment. Individual tumor responses were determined from the whole-fish brightfield and mCherry fluorescence images. Substantial differences in autofluorescence lifetime features, including optical redox ratio and mean NADH lifetime, were found between drug responsive and resistant tumors.