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

Hailey J. Knox, Jamila Hedhli, Tae Wook Kim, Kian Khalili, Lawrence W. Dobrucki and Jefferson Chan ()
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Hailey J. Knox: University of Illinois at Urbana-Champaign
Jamila Hedhli: University of Illinois at Urbana-Champaign
Tae Wook Kim: University of Illinois at Urbana-Champaign
Kian Khalili: University of Illinois at Urbana-Champaign
Lawrence W. Dobrucki: University of Illinois at Urbana-Champaign
Jefferson Chan: University of Illinois at Urbana-Champaign

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01951-0

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