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 overtreatment. 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 bright-field 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 bright-field 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. These results suggest autofluorescence lifetime imaging is predictive of anti-cancer drug response in zebrafish xenografts