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.
Highlights
Hypoxia occurs when limited oxygen supply impairs physiological functions and is a pathological hallmark of many diseases including cancer and ischemia
We present the development of Hypoxia Probe 1 (HyP-1), a hypoxia-responsive agent for PA imaging
HyP-1 can be applied to hypoxia detection in vivo, which we demonstrate with the application of a hypoxic tumor model
Summary
Hypoxia occurs when limited oxygen supply impairs physiological functions and is a pathological hallmark of many diseases including cancer and ischemia. 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. 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. Positron emission tomography (PET)-based hypoxia detection using various 18F-labeled radiotracers faces major obstacles including high background due to nonspecific uptake and limited spatial resolution[17, 18] Together, these drawbacks hamper the ability to confidently discern specific hypoxic regions using PET imaging. The PA response of HyP-1 relies on the ability of the N-oxide to modulate its optical properties
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