Development of a hybrid tracer for SPECT & optical imaging of bacterial infections

Welling M.M., A Bunschoten, Kuil J., R. Nelissen, Freek Beekman

Research output: Contribution to journalArticleScientificpeer-review

33 Citations (Scopus)

Abstract

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 asaseptic loosening of the implant, are reasons for revision of the implants. Therefore, discrimination between aseptic-mechanical-loosening and septic-bacterial-loosening of implants iscritical during selection of a patient-tailored treatment policy.Specific detection and visualization of infections is a challengebecause 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 111In (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-111was 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 99mTc-UBI29−41. Fast renal excretion of 111In-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 acombination 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.
Original languageEnglish
Pages (from-to)839-849
JournalBioconjugate Chemistry
Volume26
DOIs
Publication statusPublished - 2015

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