A Siderophore-Antibiotic Heterodimer Imaging Agent Enables <i>In Vivo</i> PET Imaging of <i>S. aureus</i> 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. There is a clinical need for improved imaging technologies to detect and characterize bacterial infections allowing for prompt initiation of treatment. We generated a molecule for positron emission tomography (PET) imaging of bacterial infection by linking two clinically used small molecules, Vancomycin (Vanco) and desferrioxamine B (DFO). 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 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 image S. aureus infection in vivo.