Technetium-99m labelled fluconazole and antimicrobial peptides for imaging of Candida albicans and Aspergillus fumigatus infections

Abstract.

The aim of this study was to investigate whether technetium-99m labelled fluconazole can distinguish fungal from bacterial infections. Fluconazole was labelled with ^99mTc and radiochemical analysis showed less than 5% impurities. The labelling solution was injected into animals with experimental infections. For comparison, we used two peptides for infection detection, i.e. UBI 29–41 and hLF 1–11, and human IgG, all labelled with ^99mTc. Mice were infected with Candida albicans or injected with heat-killed C. albicans or lipopolysaccharides to induce sterile inflammation. Also, mice were infected with Staphylococcus aureus or Klebsiella pneumoniae. Next, accumulation of ^99mTc-fluconazole and ^99mTc-labelled peptides/IgG at affected sites was determined scintigraphically. ^99mTc-fluconazole detected C. albicans infections (T/NT ratio=3.6±0.47) without visualising bacterial infections (T/NT ratio=1.3±0.04) or sterile inflammatory processes (heat-killed C. albicans: T/NT ratio=1.3±0.2; lipopolysaccharide: T/NT ratio=1.4±0.1). C. albicans infections were already seen within the first hour after injection of ^99mTc-fluconazole (T/NT ratio=3.1±0.2). A good correlation (R ²=0.864; P<0.05) between T/NT ratios for this tracer and the number of viable C. albicans was found. Although ^99mTc-UBI 29–41 and ^99mTc-hLF 1–11 were able to distinguish C. albicans infections from sterile inflammatory processes in mice, these ^99mTc-labelled peptides did not distinguish these fungal infections from bacterial infections. It is concluded that ^99mTc-fluconazole distinguishes infections with C. albicans from bacterial infections and sterile inflammations.