In Vivo Chemiluminescent Imaging Agents for Nitroreductase and Tissue Oxygenation
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- 作者：Jian Cao ; James Campbell ; Li Liu ; Ralph P. Mason ; Alexander R. Lippert
- 刊名：Analytical Chemistry
- 出版年：2016
- 出版时间：May 3, 2016
- 年：2016
- 卷：88
- 期：9
- 页码：4995-5002
- 全文大小：488K
- 年卷期：0
- ISSN：1520-6882
文摘
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.