Pathogen-specific imaging of endocarditis

• Applicant: Dr. Marvin Krohn-Grimberghe
• Subject Area: Cardiology, Angiology
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 262446245

Clinical management of acute endocarditis, a frequent and deadly infection of the heart valves, remains highly challenging and often unsuccessful. The most common pathogen in acute endocarditis is Staphylococcus aureus (S. aureus). Currently, clinical diagnosis of endocarditis relies on a combination of major and minor criteria including echocardiographic imaging, the occurrence of clinical signs such as a new heart murmur or fever, and detection of circulating bacteria in blood cultures. Blood cultures are used to determine the causative pathogen, which can often be misleading, due to false-negative as well as false-positive results. In addition, none of other diagnostic criteria can determine the causal organism. Thus, we aim to develop a clinically viable, novel method for pathogen-specific imaging of S. aureus endocarditis. Our strategy is based on the ultrahigh affinity of the virulence factor staphylocoagulase, which is secreted by the bacteria, to prothrombin and the use of this interaction to develop specific imaging probes. We will employ these probes to image murine endocarditis by hybrid ECG-triggered PET/CT and PET/MRI, thereby combining a sensitive molecular modality (PET) with a leading modality for assessing left ventricular function which can also detect valvular insufficiency (MRI). Agent development will focus on clinical feasibility to address the aforementioned urgent medical needs, with the ultimate goal of using PET/MRI detection of bacteria in valve lesions for the diagnosis of acute endocarditis in patients. We will use a previously established mouse endocarditis model, in which we induce vegetations with bacteremia after inserting a catheter through the aortic valve. The aims of the project are: a) to test the sensitivity and specificity of the method; b) to answer if the PET signal reflects bacterial population dynamics; c) to document how fast therapeutic efficacy can be seen; d) to test if the imaging technique is able to detect disease relapse; e) to show the diagnostic accuracy for septic emboli of the method.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Matthias Nahrendorf