Shrimp Used for Better Bioluminescent Cancer Imaging

Photo by the National Oceanic and Atmospheric Administration


Photo by the National Oceanic and Atmospheric Administration

Shrimp aren’t just popular on the menu. They’re also part of new technology crafted by researchers at the University of North Carolina (UNC) School of Dentistry and other institutions to better track tumor development and treatment responses in oral cancer.

“We’ve designed an imaging tool that offers researchers a way to more easily detect cancer cells and, importantly, at various stages of tumor development,” said Dr. Antonio Amelio, assistant professor at UNC’s department of dental ecology. “This provides an opportunity to better measure treatment responses and to more effectively design new therapeutic interventions.”

The design of the tool, known as the LumiFluor, adapts an enzyme called a luciferase from Oplophorus gracilirostris, a deep-sea shrimp that uses it to emit glowing blue light to confuse predators. Due to the intense light the LumiFluor generates, it is useful in preclinical studies in mice to test the effectiveness of cancer drugs.

“Other bioluminescent imaging tools are available and have been used for years. But what we have now is orders of magnitude more sensitive, meaning that you can get information earlier about the effectiveness of an investigational drug,” said Amelio, who holds a joint appointment at the university’s Lineberger Comprehensive Cancer Center.

Other imaging technologies commonly use fluorescent proteins that must be activated by an external light source such as a laser before they can produce light. But these sources can damage tissues and produce other distracting light.

Instead, the LumiFluor takes advantage of the enzymatic reaction driven by the deep-sea shrimp to produce light. It then combines the enzyme with a second fluorescent protein that absorbs light and releases it at a different wavelength.

Using this property, the researchers created versions of the LumiFluor that emit a bright green or orange light. At these wavelengths, light can more effectively penetrate tissues. And because enzymatic reactions require a substrate, which is a molecule that activates this reaction, the LumiFluor can be turned on or off like a flashlight by controlling substrate availability.

The researchers worked with structural biologists to “glue” the 2 components together and then tested the combined system’s brightness with the deep-sea shrimp enzyme alone. The LumiFluor was at least 10 times brighter than the enzyme by itself and could better penetrate tissues. It easily revealed the location of cancer cells, including those that have metastasized.

Beyond preclinical studies in mice, the researchers believe the tool could be adapted to a range of applications, including efforts to help surgeons better determine tumor margins. The LumiFluor also is being used in research on salivary gland cancers and other head and neck cancers to better understand the early stages of disease.

“In our preclinical models of head and neck cancer, if we’re able to get a better understanding of the very early stages of disease, potentially we can use this information to identify a biomarker that would allow us to diagnose disease in human patients earlier than normally possible,” said Amelio.

The study, “Fluorophore-NanoLuc BRET Reporters Enable Sensitive In Vivo Optical Imaging and Flow Cytometry for Monitoring Tumorigenesis,” was published in Cancer Research. Along with senior author Amelio, it was written by Franz X. Schaub, Weimin Li, and John L. Cleveland of the Moffitt Cancer Center and Research Institute Department of Tumor Biology; Md Shamim Reza, Sany Hoxha, and Min Guo of the Scripps Research Institute Department of Cancer Biology; Colin A. Flaveny of the Saint Louis University School of Medicine Department of Pharmacological & Physiological Science; and Adele M. Musicant of the UNC Biological and Biomedical Sciences Graduate Program, UNC at Chapel Hill.

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