Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe
- Lucas S. RyanLucas S. RyanDepartment of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United StatesMore by Lucas S. Ryan,
- Jeni GerberichJeni GerberichPrognostic Imaging Research Laboratory (PIRL), Pre-clinical Imaging Section, Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390-9058, United StatesMore by Jeni Gerberich,
- Jian CaoJian CaoDepartment of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United StatesMore by Jian Cao,
- Weiwei AnWeiwei AnDepartment of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United StatesMore by Weiwei An,
- Becky A. JenkinsBecky A. JenkinsDepartment of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United StatesMore by Becky A. Jenkins,
- Ralph P. MasonRalph P. MasonPrognostic Imaging Research Laboratory (PIRL), Pre-clinical Imaging Section, Department of Radiology, UT Southwestern Medical Center, Dallas, Texas 75390-9058, United StatesMore by Ralph P. Mason, and
- Alexander R. Lippert*Alexander R. Lippert*E-mail: [email protected]. Fax: 214-768-4089.Department of Chemistry, Center for Drug Discovery, Design, and Delivery (CD4), Center for Global Health Impact (CGHI), Southern Methodist University, Dallas, Texas 75275-0314, United StatesMore by Alexander R. Lippert
Abstract
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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This article is cited by 5 publications.
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- Krysten A. Jones, Kaitlin Kentala, Michael W. Beck, Weiwei An, Alexander R. Lippert, Jared C. Lewis, Bryan C. Dickinson. Development of a Split Esterase for Protein–Protein Interaction-Dependent Small-Molecule Activation. ACS Central Science 2019, 5 (11) , 1768-1776. https://doi.org/10.1021/acscentsci.9b00567
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