A Siderophore-Antibiotic Heterodimer Imaging Agent Enables in vivo PET Imaging of S. aureus Infections

Only a handful of bacterial strains are responsible for the majority of clinical infections, with Staphylococcus aureus being the single largest contributor. S. aureus infections can be very hard to confirm and localize. Earlier detection would allow for prompt initiation of treatment, reducing both patient morbidity and the cost to society. There is a clinical need for improved imaging technologies to detect and characterize bacterial infections. We combined our knowledge of chemistry and bacteriology to generate a molecule for positron emission tomography (PET) imaging of bacterial infection. We linked two clinically used small molecules, Vancomycin (Vanco) and desferrioxamine B (DFO), via a flexible polyethylene glycol (PEG) linker. This siderophore-antibiotic conjugate marries the high specificity of the antibiotic for Gram-positive bacteria with the receptor targeting and chelation capabilities of the siderophore. The conjugate can be labeled with 68Ga, a short-lived positron emitter, suitable for in vivo detection by PET. We report here the scalable synthesis of the heterodimeric probe [68Ga][Ga(DFO-PEG-Vanco)], the biochemical validation of its mechanism of action, its biodistribution, and the ability to distinguish between S. aureus or sterile inflammation in vivo.