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