New contrast allows whole-body blood clot scans in animal model.


A blood clot is a dangerous health situation with the potential to trigger heart attacks, strokes and other medical emergencies. To treat a blood clot, doctors need to find its exact location. However, current clinical techniques can only look at one part of the body at a time, slowing treatment and increasing the risk for complications. Now, researchers from Massachusetts General Hospital are reporting a method, tested in rats, that may someday allow health care providers to quickly scan the entire body for a blood clot.  The team will describe their approach at the 250th National Meeting & Exposition of the American Chemical Society (ACS).

Previous studies show that if a person suffers a stroke that stems from a blood clot, their risk for a second stroke skyrockets. The initial blood clot can break apart and cause more strokes if it is not quickly found and treated. Depending on where the blood clot is located, the treatment varies, some patients respond well to drugs, while others are better addressed with surgery.

To locate a blood clot, earlier studies show that a physician may need to use three different methods, ultrasound to check the carotid arteries or legs, magnetic resonance imaging (MRI) to scan the heart and computed tomography to view the lungs.  The team explain that patients could end up being scanned multiple times by multiple techniques in order to locate a clot. Therefore, researchers have been seeking a method that could detect blood clots anywhere in the body with a single whole-body scan.

In previous studies from the lab, results identified a peptide that binds specifically to fibrin, an insoluble protein fiber found in blood clots. In the current study, they developed a blood clot probe by attaching a radionuclide to the peptide. The researchers state that radionuclides can be detected anywhere in the body by an imaging method called positron emission tomography (PET). The current 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 blood clots. The team ultimately constructed and tested 15 candidate blood clot probes.

The researchers first analyzed how well each probe bound to fibrin in a test tube, and then they studied how well the probe detected blood clots in rats.  Data findings show that the probes all had a similar affinity to fibrin in vitro, however, in rats their performances were notably different.  The lab attributed these differences to metabolism. Results show that some probes were broken down quickly in the body and could no longer bind to blood clots, however, others were resistant to metabolism.  The researchers conclude that the best probe was  called FBP8, which stands for ‘fibrin binding probe #8’, it contained copper-64 as the radionuclide and was the most stable.

For the future the team is moving forward into the next phase of research with this best-performing probe.The group is hoping to start testing the probe in human patients in the fall.  However, the group note that it could take an additional five years of research before the probe is approved for routine use in a clinical setting.

Source:   American Chemical Society

 

The whole body of a rat can be imaged for blood clots with one PET scan (which is overlaid here on an MRI image) using the FBP8 probe. Arrow points to a blood clot.  Credit: Peter Caravan, Ph.D.

The whole body of a rat can be imaged for blood clots with one PET scan (which is overlaid here on an MRI image) using the FBP8 probe. Arrow points to a blood clot. Credit: Peter Caravan, Ph.D.

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