The new probe - shown here in a rat - should allow blood clots to be located with a single, whole-body PET scan.
Image credit: Peter Caravan
The new probe - developed by researchers at Massachusetts General Hospital (MGH) in Boston - featured at the national meeting of the American Chemical Society (ACS) earlier this week.
A blood clot is a serious, potentially fatal, medical condition. The faster a clot is found, the better the chances it can be removed before it triggers a heart attack, stroke, or other medical emergency.
If a person has a stroke because of a clot, the risk of another stroke increases hugely. The clot can break up and cause more strokes. Also, treatments vary, depending on where the clot is located. Some require surgery, while others may respond to clot-busting drugs.
Thus, in order to treat a blood clot, doctors have to find its precise location in the body, and quickly. But current methods only allow them to look at one part of the body at a time, using different types of scan.
For example, it may be necessary to have the patient undergo three different types of scan: ultrasound to check the carotid arteries or legs, magnetic resonance imaging (MRI) to look at the heart, and computed tomography (CT scan) to examine the lungs.
"It's a shot in the dark," says Peter Caravan, an assistant in chemistry at MGH and associate professor in radiology at Harvard Medical School. In order to locate the clot, the patient could end up being scanned several times using different methods, so the team "sought a method that could detect blood clots anywhere in the body with a single whole-body scan."
Prof. Caravan and his team had already found a peptide that binds specifically to fibrin - an insoluble protein fiber that is present in blood clots.
For their latest work, they attached a radionuclide to the peptide. Radionuclides are small doses of radioactive isotopes used in an imaging method called positron emission tomography (PET). PET scans can highlight radionuclides anywhere in the body.
FBP8 most stable probe
The team tested many different combinations of radionuclides, peptides, and ways of linking them together, to find the ones that were most likely to give the brightest PET images in blood clots.
A total of 15 candidate blood clot probes were identified. After analyzing how well they bound to fibrin in test tubes, the researchers then tested them in blood clots in rats.
The results showed how different test tube results can be compared with what happens in the body, as Prof. Caravan explains:
"The probes all had a similar affinity to fibrin in vitro, but, in rats, their performances were quite different."
The researchers suggest the difference was because in the body, the probes are subject to metabolism, which breaks down some of the probes, while others are able to withstand it.
A probe that the team calls FBP8, short for "fibrin binding probe #8," which has copper-64 as the radionuclide, was the most stable.
Now the big question, says Prof. Caravan, is "how well will these perform in patients?" The team plans to start testing FBP8 in humans in the fall, and suggests it could be another 5 years before it is approved for clinical use.