The probe's main ingredient is a molecule that labels active proteases - protein-destroying enzymes - that run amok in cancerous cells. The molecule is normally invisible to the naked eye but it carries a fluorescent tag that lights up when it binds to the protease. The tag beams out near-infrared light that passes through skin and is detectable with a special camera. The use of the imaging technique in mice is described in a study to be published in the Sept. 9 advance online issue of Nature Chemical Biology.
"Nowadays the detection of cancer, breast cancer for instance, is normally done by mammography, using X-rays - which might actually increase your risk of cancer. We think these probes may ultimately provide a less harmful, noninvasive method of detecting cancer," said the article's lead author Galia Blum, PhD, a postdoctoral scholar in the laboratory of Matthew Bogyo, PhD, assistant professor of pathology.
And that's just for starters.
"It's neat. The next generation of our experiments will apply the probes during surgery," said Bogyo, the study's senior author. "It would be nice to 'paint' it on tissues so you could distinguish between tumor and non-tumor."
A key advantage of this enzyme-targeting molecule is its size. About 100 times smaller than other molecular imaging reporters, it can easily slip across the cell membrane and enter living cells. It can also move through the animal quickly, which opens up the possibility of using the technique to light up tumors while surgery is in progress.
"Unlike other enzyme-targeting molecules, it's very specific, sticks to where it binds and does it all very rapidly - in 30 minutes or less," Bogyo said.
And unlike most other molecular probes, this type identifies only active enzymes. "We went one step beyond just telling if the enzymes are there. We can answer the question, 'Are they active"' That's important because an accumulation of inactive enzymes doesn't necessarily indicate disease," Blum said.
Bogyo, Blum and colleagues designed the probe to bind to a subset of a family of proteases called cysteine cathepsins, which are more active in several types of cancer as well as other diseases. Now they are tinkering with the probe's configuration in an effort to create a variant that recognizes the enzymes involved in apoptosis, the process of cell death. This could ultimately allow researchers and doctors to visualize response to chemotherapy in tumors, Bogyo said.
And because other diseases besides cancer involve hyped-up proteases - such as Alzheimer's, arthritis, atherosclerosis and osteoporosis - the approach might be of use in diagnosing and treating them as well.
The work went surprisingly smoothly because of Blum's background in chemistry as well as biology. Using her chemistry skills, she created the probes. Then she switched to biology mode and tested them. When she discovered that an earlier version of the probe worked great in tissue culture but decomposed on contact with mouse blood, she was able to tweak the molecule's structure to survive inside a living animal.
In addition to the potential health-care applications, the approach provides a valuable research tool, the researchers said. "It allows you to see exactly where enzymes are active within living animals," said Bogyo.
The Stanford researchers' ultimate goal is to test it in humans, though they'll complete more testing in animals before requesting permission from the U.S. Food and Drug Administration to conduct a human trial. "Since there are currently no fluorescent imaging agents in use in humans, the approval process is likely to require significantly more preclinical data," Bogyo said.
In preparation, they are working with James Basilion, PhD, associate professor of biomedical engineering at Case Western Reserve University, who is using the probe in surgical procedures in animals. They are now testing the probe's ability to reveal the presence of glioma tumor cells during brain surgery in mice.
"Because glioma tumor tissue looks nearly identical to normal tissue, it's very difficult for surgeons to remove every last bit of it," said Bogyo. "We think this will help."
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research