Image by Andre E.X. Brown
BOSTON—Researchers have devised a method that may someday allow healthcare providers to quickly scan the entire body for a blood clot.
The team developed a fibrin-specific probe, known as 64Cu-FBP8, by attaching a radionuclide to a fibrin-binding peptide.
They administered the probe to rats with thrombosis and found they could locate clots via PET imaging.
Peter Caravan, PhD, of the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Boston, presented details on this work at the 250th National Meeting & Exposition of the American Chemical Society.
He and his colleagues also reported results with this method in Arteriosclerosis, Thrombosis, and Vascular Biology.
Dr Caravan noted that, at present, a physician may need to use 3 different methods to locate a blood clot: ultrasound to check the carotid arteries or legs, MRI to scan the heart, and CT to view the lungs.
“It’s a shot in the dark,” he said. “Patients could end up being scanned multiple times by multiple techniques in order to locate a clot. We sought a method that could detect blood clots anywhere in the body with a single, whole-body scan.”
He and his colleagues reported results with an early prototype of their fibrin-specific probe in 2011. With the current work, they believe they have optimized the probe, and they are now ready to proceed to clinical studies.
The researchers used different radionuclides and peptides, as well as different chemical groups for linking the radionuclide to the peptide, to identify which combination would provide the brightest PET signal in clots. They ultimately constructed and tested 15 candidate probes.
The team first analyzed how well each probe bound to fibrin in vitro. Then, they studied how well the probe detected thrombi in rats.
“The probes all had a similar affinity to fibrin in vitro, but, in rats, their performances were quite different,” Dr Caravan said.
He attributed these differences to metabolism. Some probes were broken down quickly in the body and could no longer bind to a thrombus, but others were resistant to the metabolism.
Dr Caravan said the best probe was the one that was most stable. And that proved to be 64Cu-FBP8 (copper-64—fibrin binding probe #8).
To test 64Cu-FBP8 in rats, the researchers induced thrombosis via ferric chloride application on both the carotid artery and femoral vein. They then performed 64Cu-FBP8-PET/CT imaging 1, 3, or 7 days after thrombosis induction.
The team found they could locate arterial and venous thrombi on fused PET/CT images with 97.6% accuracy. A single, whole-body PET/MRI could reveal the location of both arterial and venous thrombi as well.
Dr Caravan said the question now is how well this method will work in humans. To answer that, his group is hoping to start testing the probe in clinical trials in the fall.
