In Vivo Chemiluminescent Imaging Agents for Nitroreductase and Tissue Oxygenation

Jian Cao, James Campbell, Li Liu, Ralph P. Mason, Alexander R. Lippert

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4995-5002
Number of pages8
JournalAnalytical Chemistry
Issue number9
StatePublished - May 3 2016

ASJC Scopus subject areas

  • Analytical Chemistry


Dive into the research topics of 'In Vivo Chemiluminescent Imaging Agents for Nitroreductase and Tissue Oxygenation'. Together they form a unique fingerprint.

Cite this