New fluorescent protein lights up internal organs

Ashley N. Paddock, ashley.paddock@photonics.com

A new fluorescent protein that helps scientists to “see” clearly the internal organs of living animals – without the need for imaging techniques that pose side effects – could be a breakthrough in whole-body imaging.

Researchers use various techniques to image the internal organs of people and animals, but each has potential side effects. X-rays and computed tomography scanning, for instance, involve exposure to radiation. Although magnetic resonance imaging is safer, subjects must ingest contrasting agents to make internal body structures more visible.

Liver cells in this mouse contain the new fluorescent protein iRFP. The mouse was exposed to near-infrared light, which causes the iRFP to emit light waves in the near-IR. The images – from the back (left) and right side (right) – show the fluorescent near-IR waves passing readily through the mouse’s tissue to reveal its brightly glowing liver.

To sidestep these limitations, researchers from Albert Einstein College of Medicine of Yeshiva University have developed iRFP, a phytochrome-based fluorescent protein. Created in the lab of Dr. Vladislav Verkhusha, associate professor of anatomy and structural biology, the protein is based on a bacterial phytochrome, a pigment used by certain bacteria to detect light. Unlike other fluorescent proteins, which absorb red, blue, green and other wavelengths, iRFP absorbs and emits near-IR light. Mammalian tissues and hemoglobin are nearly transparent in these wavelengths, so they do not obscure images of cells tagged with the protein.

To test the new protein, the researchers injected mice with adenovirus particles containing the gene for iRFP. Once the particles reached and infected the liver, the infected cells expressed that gene, producing the iRFP protein. The mice then were exposed to near-IR light, and their fluorescent livers easily were imaged using a whole-body imaging device. The investigators detected the fluorescent liver the second day after infection and observed that it reached a peak at day five. Subsequent experiments indicated that iRFP is nontoxic.

The new method not only produced a far brighter image than other fluorescent proteins used to visualize the liver of live animals, but also had a higher contrast and proved to be stable over time, according to the study, which was published online July 17 in Nature Biotechnology (doi: 10.1038/nbt.1918).

Verkhusha hopes that the new protein will broaden the potential uses for noninvasive whole-body imaging, for imaging internal tumor growth, for the spread of infection and for tracking tissue development and regeneration.