In
trauma and
orthopedic surgery,
infection of implants has a major impact on the outcome for patients.
Infections may develop either during the initial implantation or during the lifetime of an implant. Both
infections, as well as aseptic loosening of the implant, are reasons for revision of the implants. Therefore, discrimination between aseptic-mechanical-loosening and septic-bacterial-loosening of implants is critical during selection of a patient-tailored treatment policy. Specific detection and visualization of
infections is a challenge because it is difficult to discriminate
infections from
inflammation. An imaging tracer that facilitates bacterial identification in a pre- and intraoperative setting may aid the workup for patients suspicious of
bacterial infections. In this study we evaluated an
antimicrobial peptide conjugated to a hybrid label, which contains both a
radioisotope and a
fluorescent dye. After synthesis of DTPA-Cy5-UBI29-41 and-when necessary-radiolabeling with (111)In (yield 96.3 ± 2.7%), in vitro binding to various bacterial strains was evaluated using radioactivity counting and confocal fluorescence microscopy. Intramuscular
bacterial infections (S. aureus or K. pneumoniae) were also visualized in vivo using a combined nuclear and fluorescence imaging system. The
indium-111 was chosen as label as it has a well-defined coordination chemistry, and in pilot studies labeling DTPA-Cy5-UBI29-41 with technetium-99m, we encountered damage to the
Cy5 dye after the reduction with SnCl2. As a reference, we used the validated tracer (99m)Tc-UBI29-41. Fast renal excretion of (111)In-DTPA-Cy5-UBI29-41 was observed. Target to nontarget (T/NT) ratios were highest at 2 h post injection: radioactivity counting yielded T/NT ratios of 2.82 ± 0.32 for S. aureus and 2.37 ± 0.05 for K. pneumoniae. Comparable T/NT ratios with fluorescence imaging of 2.38 ± 0.09 for S. aureus and 3.55 ± 0.31 for K. pneumoniae were calculated. Ex vivo confocal microscopy of excised infected tissues showed specific binding of the tracer to bacteria. Using a combination of nuclear and fluorescence imaging techniques, the hybrid
antimicrobial peptide conjugate DTPA-Cy5-UBI29-41 was shown to specifically accumulate in
bacterial infections. This hybrid tracer may facilitate integration of noninvasive identification of
infections and their extent as well as real-time fluorescence guidance during surgical resection of infected areas.