Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe.

Authors:
Jeni Gerberich
Jeni Gerberich
UT Southwestern Medical Center
Jian Cao
Jian Cao
Stony Brook University
Stony Brook | United States
Weiwei An
Weiwei An
Key Laboratory of Systems Biology
Ralph P Mason
Ralph P Mason
University of Texas Southwestern Medical Center
United States
Alexander R Lippert
Alexander R Lippert
University of California
United States

ACS Sens 2019 Apr 30. Epub 2019 Apr 30.

Prognostic Imaging Research Laboratory (PIRL), Pre-clinical Imaging Section, Department of Radiology , UT Southwestern Medical Center , Dallas , Texas 75390-9058 , United States.

Oxygenation and tissue hypoxia play critical roles in mammalian biology and contribute to aggressive phenotypes in cancerous tumors, driving research to develop accurate and easy-to-implement methods for monitoring hypoxia in living cells and animal models. This study reports the chemiluminescent probe HyCL-4-AM, which contains a nitroaromatic sensing moiety and, importantly, an acetoxymethyl (AM) ester that dramatically improves operation in cells and animals. HyCL-4-AM provides a selective 60 000-fold increase in luminescence emission in the presence of rat liver microsomes (RLM). For cellular operation, the chemiluminescence response kinetics is sharply dependent on oxygen levels, enabling highly significant and reproducible measurement of hypoxia in living cells. Whole animal imaging experiments in muscle tissue and tumor xenografts show that HyCL-4-AM can differentiate between well oxygenated muscle tissue and hypoxic tumors, demonstrating potential for monitoring tumor reoxygenation via hyperoxic treatment.

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Source
http://dx.doi.org/10.1021/acssensors.9b00360DOI Listing
April 2019

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