Trimodal X-ray, luminescence, and fluorescence imaging of bacterial infection responsive myeloperoxidase activity in mice

1588 Objectives To localize Staphylococcus aureus (S. aureus) and the bacterial infection responsive myeloperoxidase (MPO) enzyme activity in vivo. Methods Multimodal imaging of mice challenged earlier with S.aureus were used to obtain X-ray contrast, luminescence, and near infrared fluorescence (NIRF) images. Three different non-radioactive agents, luminol (i.p), visipaque (i.v.), and a fluorescent probe containing a bis(zinc2+dipicolylamine, Zn-DPA) motif (i.v.) were administered under anesthesia after 24 hrs after infection. An imaging system, which combines optical imaging and digital X-ray imaging, was used to obtain anatomical localization of the fluorescence and luminescence signals. Results The luminescence molecular signals, a byproduct of MPO enzyme action co localized in vivo with the X-ray contrast signals of the radiopaque agents collected at the urinary bladder. The NIRF molecular signals of Zn-DPA-fluoroprobe, a motif, which binds with high affinity to apoptotic, necrotic, and bacterial surfaces were not present at the bladder. However robust binding of the fluorescence probe was observed at the liver. Conclusions A combined luminescence, fluorescence, and radiopaque signals aided in the determination of the increased MPO activity at the bladder with relatively little bacteria interacting fluoroprobe in the vicinity. The MPO activity corresponds to the neutrophil activation as a bacterial infection response. This initial immune response shows stark similarities with the mechanism suggested recently for Myobacterium bovis bacillus Calmette-Guerin (BCG) treatment of cancer of the bladder