Translation of ceragenin affinity for bacteria to an imaging reagent for infection

Responses to bacterial infections may be manifest systemically without evidence of the location of the infection site. A rapid means of pinpointing infection sites would be useful in providing effective and possibly localized treatment. Successful means of identifying infection sites would require two components: (1) a molecule capable of recognizing bacteria and (2) a means of communicating recognition. For the recognition element, we used a ceragenin, a small molecule with affinity for bacterial membranes that was designed as a mimic of endogenous antimicrobial peptides. For the communication element, we used ⁶⁴Cu, which is a positron emitter. By conjugating a copper chelating group to the ceragenin, the two elements were combined. Chelation of ⁶⁴Cu by the conjugate was effective and provided a stable complex that allowed in vivo imaging. When administered to mice in a thigh infection model, the ⁶⁴Cu-labeled conjugate accumulated at the site of infection (right thigh) without accumulation at the complementary site (left thigh). This conjugate may provide a means of identifying infection sites in patients presenting general signs of infection without localized symptoms.