Heterogeneity in tumor chromatin-doxorubicin binding revealed by in vivo fluorescence lifetime imaging confocal endomicroscopy.

ABSTRACT: We present an approach to quantify drug-target engagement using in vivo fluorescence endomicroscopy, validated with in vitro measurements. Doxorubicin binding to chromatin changes the fluorescence lifetime of histone-GFP fusions that we measure in vivo at single-cell resolution using a confocal laparo/endomicroscope. We measure both intra- and inter-tumor heterogeneity in doxorubicin chromatin engagement in a model of peritoneal metastasis of ovarian cancer, revealing striking variation in the efficacy of doxorubicin-chromatin binding depending on intra-peritoneal or intravenous delivery. Further, we observe significant variations in doxorubicin-chromatin binding between different metastases in the same mouse and between different regions of the same metastasis. The quantitative nature of

SUBMITTER: Sparks H 

PROVIDER: S-EPMC6037736 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature