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Labeled Prothrombin to Detect Bacterial Endocarditis

August 22nd, 2011 Stanley Darma News

Researchers from Massachusetts General Hospital have successfully explored the possibility of using prothrombin to identify coagulase-positive Staphylococcus aureus-associated endocarditis. In their study they used an engineered radio-labeled analog of prothrombin as an imaging probe to detect S. aureus vegetations on heart valves of mice using PET-CT.

In their search for a targeted imaging strategy, they exploited the ability of S. aureus to clot human blood. Staphylocoagulase, an enzyme secreted by S. aureus bacteria, binds prothrombin and after activating it, it forms a staphylocoagulase-prothrombin complex which has all the fibrinogen-clotting abilities, but is not affected by physiologic thrombin inhibitors. Knowing this, the investigators engineered prothrombin analogs as imaging probes. Eventually they were able to detect the radio-labeled agents deposited into S. aureus-induced vegetations with PET-CT. This shows promise for future use in human patients, if the researchers succeed in developing this technique further and are able to acquire regulatory approval for it.

Image: PET-CT image of S. aureus endocarditis. Images A and B show a molecular model of how the PET reporter (yellow structure with colored spheres) binds to the target, the bacterial enzyme staphylocoagulase (violet). Image B is rotated 90 degrees relative to image A. CT (images C and D) and PET-CT (images E and F) show location of the radiolabeled prothrombin in vegetations (arrowhead) around the aortic valve (asterisk) of a mouse heart. Images G-I show location of the PET agent in aortas of mice with (G-H) and without (I-J) S. aureus endocarditis.

Link: Imaging probe allows noninvasive detection of dangerous heart-valve infection …

Abstract in Nature Medicine: In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation

Stanley Darma

Stanley is an MD and PhD candidate at the Academic Medical Center Amsterdam, the Netherlands. His research field is in ophthalmology and optical coherence tomography, making amazing pictures of and performing precise measurements in the human retina everyday.

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