Serial monitoring of human systemic and xenograft models of leukemia using a novel vascular disrupting agent.

Leukemia
M BenezraM S Bradbury

Abstract

Advances in the treatment of acute leukemia have resulted in significantly improved remission rates, although disease relapse poses a significant risk. By utilizing sensitive, non-invasive imaging guidance, detection of early leukemic infiltration and the extent of residual tumor burden after targeted therapy can be expedited, leading to more efficient treatment planning. We demonstrated marked survival benefit and therapeutic efficacy of a new-generation vascular disrupting agent, combretastatin-A1-diphosphate (OXi4503), using reporter gene-imaging technologies and mice systemically administered luc+ and GFP+ human leukemic cells (LCs). Before treatment, homing of double-transduced cells was serially monitored and whole-body cellular distributions were mapped using bioluminescence imaging (BLI). Imaging findings strongly correlated with quantitative GFP expression levels in solid organs/tissues, suggesting that the measured BLI signal provides a highly sensitive and reliable biomarker of tumor tissue burden in systemic leukemic models. Such optical technologies can thereby serve as robust non-invasive imaging tools for preclinical drug discovery and for rapidly screening promising therapeutic agents to establish potency, treat...Continue Reading

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Citations

Jul 19, 2013·Nature Communications·Paul GuilhamonStephan Beck
Feb 24, 2016·Experimental Hematology·Raphael C BosseChristopher R Cogle
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Jul 12, 2021·Experimental Hematology & Oncology·Yiyi YaoHuafeng Wang

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