A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia

Hailey J. Knox, Jamila Hedhli, Tae Wook Kim, Kian Khalili, Lawrence W. Dobrucki, Jefferson Chan

Research output: Contribution to journalArticlepeer-review


Hypoxia occurs when limited oxygen supply impairs physiological functions and is a pathological hallmark of many diseases including cancer and ischemia. Thus, detection of hypoxia can guide treatment planning and serve as a predictor of patient prognosis. Unfortunately, current methods suffer from invasiveness, poor resolution and low specificity. To address these limitations, we present Hypoxia Probe 1 (HyP-1), a hypoxia-responsive agent for photoacoustic imaging. This emerging modality converts safe, non-ionizing light to ultrasound waves, enabling acquisition of high-resolution 3D images in deep tissue. HyP-1 features an N-oxide trigger that is reduced in the absence of oxygen by heme proteins such as CYP450 enzymes. Reduction of HyP-1 produces a spectrally distinct product, facilitating identification via photoacoustic imaging. HyP-1 exhibits selectivity for hypoxic activation in vitro, in living cells, and in multiple disease models in vivo. HyP-1 is also compatible with NIR fluorescence imaging, establishing its versatility as a multimodal imaging agent.

Original languageEnglish (US)
Article number1794
JournalNature communications
Issue number1
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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