5/29/2018 IHSI
“We know that a lot of tumors are hypoxic, so many new treatments have been developed that become activated in low-oxygen conditions. But these treatments have been inconsistent in clinical trials, because not all tumors are hypoxic.”
Written by IHSI
Jefferson Chan, PhD, is an assistant professor in the Department of Chemistry in the College of Liberal Arts and Sciences. According to their website, research in Prof. Jefferson Chan’s lab group “lies at the interface of chemistry, biology, and medicine.” There are several research interests his lab group explores; summarized, they include the development of small-molecule and protein-based sensors for non-invasive molecular imaging, the preparation of new diagnostics and therapeutics for infectious diseases, and synthetic organic chemistry. The first of these interests—development of small molecular and protein-based sensors—looks to have applications to impact several different neurological medical conditions.
Non-invasive photoacoustic imaging for acute hypoxia
Hypoxia, which happens when tissue is oxygen-deprived, is indicative of blockages or narrowing in blood vessels, which often lead to stroke or peripheral artery disease. Chan and his team have developed an oxygen-sensitive molecule probe that emits ultrasound signals in response to light—a process called photoacoustic imaging. The imaging technique can be done in real time, non-invasively, at a higher resolution and lower cost than the current clinical standard.
“In a clinical setting, you would take a regular ultrasound machine and equip it with a light source—you can buy LEDs for around $200 that are powerful enough and safe for clinical applications,” says Chan. Physicians would administer the photoacoustic molecules to the patient by injection, then use the ultrasound machine to get a visual of the hypoxic tissue area.
The oxygen-detecting molecular probe has been tested on cell cultures and in mice, so far. Chan and researchers have found that their photoacoustic technique can find hypoxia mere minutes after a mouse’s artery was constricted, showing promise for quickly finding stroke sites or blood clots in tissue.
Additionally, neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by a decline in cognitive abilities that result from neuronal cell death. Hypoxia, oxidative stress, metal ion signaling, and neurotransmission are all believed to play a role in the neuropathology of AD. Chan says their interplay is inadequately studied, especially in the context of in vivo biological systems, so his group plans to modify and further design these chemical and protein-based probes to discover the mechanisms underlying AD. His group has also applied photoacoustic imaging to tumor tissue.
“We know that a lot of tumors are hypoxic, so many new treatments have been developed that become activated in low-oxygen conditions. But these treatments have been inconsistent in clinical trials, because not all tumors are hypoxic,” Chan says. “This gives scientists and physicians a way to non-invasively look inside tumors and determine whether a patient’s tumor is hypoxic and they would be a good candidate for a certain drug, or should go with a different treatment plan.”
For more details on this research, see the paper “A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia” available in the online journal Nature Communications.