Vancomycin-based tracers for bacteria-targeted imaging of infection

Bacterial infections are a major problem in virtually all medical disciplines. These infections are often misdiagnosed or mistreated, which can result in severe complications like prolonged hospitalization, loss of limbs, or even death. Current medical imaging methods used for the detection of bacterial infections often struggle to distinguish infection from inflammation. Better detection methods are needed, as early and accurate detection of infections can greatly improve patient outcomes. In this thesis, we developed a strategy for non-invasive detection of bacteria through the natural ability of the antibiotic vancomycin to bind Gram-positive bacteria, which are common culprits in orthopedic and trauma-related infections. By attaching a radioactive marker (fluorine-18) to vancomycin, it is possible to visualize the accumulation of these novel tracers using positron emission tomography at sites of infection. This allows doctors to visualize the bacterial infection, something that remains difficult with current clinical methods.

A total of three vancomycin-based tracers was developed and tested. Two of these tracers had high affinity for the bacterium Staphylococcus aureus, a notorious causative agent of joint and bone infections. These novel tracers were further tested, both in lab settings and animal infection models. We were able to demonstrate their potential to accumulate at the site of infection, making it possible to distinguish between infection and sterile inflammation.

This research paves the way for more accurate, targeted, and non-invasive imaging of infection, with the ultimate goal of optimizing these tracers for future clinical application to improve patient care.