Imaging of Infections: switch on the light:Development and evaluation of novel tracers for optical molecular fluorescence imaging

Despite major advances in medicine and patient care, infections remain a great threat to human health. This is exacerbated by increasing rates of surgical interventions and the rapid increment of antimicrobial resistance that poses challenges for effective therapeutic interventions. Current diagnostic tools for infection detection, such as molecular and culturing techniques, are time-consuming and rely on the collection of clinical samples which is not always possible. Furthermore, there is a great need for improvement of the diagnosis and treatment of infections at early stages. In this context, imaging is an attractive approach to localize sites of infection. However, traditional imaging modalities, such as radiography, are non-specific and unable to distinguish infection from sterile inflammation. To solve this specificity challenge, targeted molecular imaging, based on the use of specific tracers, has emerged. This approach enables specific, non-invasive and real-time visualization of causative pathogens. Accordingly, the aim of the research described in this PhD thesis was to develop novel tracers for targeted fluorescence imaging of infections, and to evaluate optical fluorescence imaging for the detection of infections at early stages. To achieve these objectives, the evaluation of novel fluorescent tracers was performed through in vitro, ex vivo and in vivo analyses following various clinical settings, such as fluorescence-guided arthroscopy or fluorescence-guided bronchoscopy. The results demonstrate the potential of targeted fluorescence imaging for early detection of Gram-positive bacterial and fungal infections, and highlight the importance of targeted imaging to accelerate the time-to-result between diagnosis and treatment, which is crucial for successful infection management