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In Vivo Chemiluminescent Imaging Agents for Nitroreductase and Tissue Oxygenation.
- Source :
-
Analytical Chemistry . 5/3/2016, Vol. 88 Issue 9, p4995-5002. 8p. - Publication Year :
- 2016
-
Abstract
- Tissue oxygenation is a driving parameter of the tumor microenvironment, and hypoxia can be a prognostic indicator of aggressiveness, metastasis, and poor response to therapy. Here, we report a chemiluminescence imaging (CLI) agent based on the oxygen-dependent reduction of a nitroaromatic spiroadamantane 1,2-dioxetane scaffold. Hypoxia ChemiLuminescent Probe 2 (HyCL-2) responds to nitroreductase with ~170-fold increase in luminescence intensity and high selectivity for enzymatic reductase versus other small molecule reductants. HyCL-2 can image exogenous nitroreductase in vitro and in vivo in living mice, and total luminescent intensity is increased by ~5-fold under low oxygen conditions. HyCL-2 is demonstrated to report on tumor oxygenation during an oxygen challenge in H1299 lung tumor xenografts grown in a murine model as independently confirmed using multispectral optoacoustic tomography (MSOT) imaging of hemoglobin oxygenation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00032700
- Volume :
- 88
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Analytical Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 115724959
- Full Text :
- https://doi.org/10.1021/acs.analchem.6b01096