Researchers created and tested a targeted contrast agent capable of detecting blood clots in the hearts of patients suffering from atrial fibrillation, or an irregular heartbeat. The strategy could also be used to detect clots in other parts of the body, such as vessels that, when blocked, can cause a stroke.
Atrial fibrillation, defined as an irregular and often rapid heart rate, is a common condition that can lead to the formation of clots in the heart, which can then dislodge and flow to the brain, potentially resulting in a stroke. The standard method of detecting these clots involves seizing the patient and inserting a fairly large tube down the throat and esophagus for a transesophageal ultrasound. Researchers at Massachusetts General Hospital (MGH) have now developed and tested a targeted contrast agent for noninvasive detection and imaging of these clots. In a study published in JACC: Cardiovascular Imaging, they confirmed the efficacy of this strategy.
The agent has a high affinity for fibrin, a protein found in blood clots, and is detected using a radioactive copper tag. “The idea behind the technology is that the agent will find and bind to blood clots anywhere in the body not just the heart and make the clots detectable like a bright star in the night sky,” says senior author David Sosnovik, MD, FACC, director of MGH’s Martinos Center for Biomedical Imaging and associate professor of Medicine at Harvard Medical School.
The idea behind the technology is that the agent will find and bind to blood clots anywhere in the body not just the heart and make the clots detectable like a bright star in the night sky.
David Sosnovik
“In some ways, this is similar to conducting a smart search on a search engine like Google, where the search terms used guide the search. The agent is injected into a small peripheral vein and circulates throughout the human body in search of clots.” If it doesn’t find any clots, it’s quickly excreted from the body; however, if it does find a clot and binds to it, clinicians can detect it using positron emission tomography, an imaging technique.
Sosnovik and his colleagues first investigated how the agent reacts in eight healthy volunteers (specifically, its metabolism and pharmacokinetics). The agent was initially stable within the body after injection and then cleared from tissues within several hours, indicating that it was safe. The agent was then given to patients with atrial fibrillation, some of whom had clots in their hearts and others who did not. Imaging tests on the heart revealed bright signals within the clots that were not visible in patients who did not have clots.
“Of course, much more work and many more studies will need to be done before this changes routine clinical practice,” says Sosnovik, “but this first-in-human study is an important step.” “Most importantly, this intelligent or molecularly targeted agent can detect clots anywhere in the body.”
Sosnovik emphasized that the project’s multidisciplinary nature was critical to its success, with critical roles played by a variety of scientists, including Peter Caravan, PhD, who invented and developed the study’s agent and is the co-director of MGH’s Institute for Innovation in Imaging. “This probe was invented and optimized in my laboratory by a dedicated team of chemists and biologists with funding from the National Heart, Lung, and Blood Institute of the National Institutes of Health,” Caravan says. “It’s extremely satisfying to see these years of work pay off with a fibrin-specific PET probe that has the potential to make a real difference in human health.”
David Izquierdo-Garcia, PhD, an assistant in Biomedical Engineering at MGH, and Ciprian Catana, MD, PhD, director of Integrated MR-PET Imaging at MGH’s Martinos Center for Biomedical Imaging, were also key players in the study. Izquierdo-Garcia, the paper’s lead author, and Catana both emphasized the novel nature of the imaging platform used in the study. “Not only did we use a novel molecular imaging probe in humans for the first time,” says Izquierdo-Garcia, “but this is also one of the first studies to fully explore the synergies and advantages of integrated PET-MRI scanners.”
“Working at the Martinos Center for Biomedical Imaging and being part of multidisciplinary teams that collaborate to develop and apply cutting-edge imaging technologies is a privilege,” Catana adds. “We were the first facility in the United States to install a fully integrated PET-MRI scanner, and we have played a significant role in the advancement and clinical translation of this technology.”
