Radiolabeled Bacterial Metallophores as Targeted PET Imaging Contrast Agents for Accurate Identification of Bacteria and Outer Membrane Vesicles in vivo

Modern technologies such as 16s DNA sequencing capable of identifying microbes and provide taxonomic resolution at species and strain-specific levels is destined to be transformative1. Likewise, there is an emerging need to accurately identify both infectious and non-infectious microbes non-invasively in the body at the genus and species level to guide diagnosis and treatment strategies. Here, we report development of radiometal-labelled bacterial chelators, knowns as metallophores that allow non-invasive and selective imaging of bacteria and bacterial products in vivo. We show that these novel contrast agents are able to identify E. coli with strain level specificity and other bacteria, such as K. pneumoniae, based on expression of distinct cognate transporters on the bacterial surface. The probe is also capable of tracking probiotic, engineered bacteria and bacterial products, outer membrane vesicles (OMVs), in unique niches such as tumours. Moreover, we report that this novel targeted imaging approach has impactful applicability in monitoring antibiotic treatment outcomes in patients with pulmonary infections, thereby providing the ability to optimize individualized therapeutic approaches. Compared to traditional techniques used to manufacture probes, this strategy simplifies the process considerably by combining the function of metal attachment and cell recognition into a single molecule. Thus, we anticipate that these probes will be widely used in both clinical and investigative settings in living systems for non-invasive imaging of infectious and non-infectious organisms.