title: 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 (99m)Tc 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 (99m)Tc. 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 (99m)Tc-fluconazole and (99m)Tc-labelled peptides/IgG at affected sites was determined scintigraphically. (99m)Tc-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 (99m)Tc-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 (99m)Tc-UBI 29-41 and (99m)Tc-hLF 1-11 were able to distinguish C. albicans infections from sterile inflammatory processes in mice, these (99m)Tc-labelled peptides did not distinguish these fungal infections from bacterial infections. It is concluded that (99m)Tc-fluconazole distinguishes infections with C. albicans from bacterial infections and sterile inflammations.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, The Netherlands.
authors.forename: Antonella
authors.initials: A
authors.lastname: Lupetti
authors.forename: Mick M
authors.initials: MM
authors.lastname: Welling
authors.forename: Ulderico
authors.initials: U
authors.lastname: Mazzi
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nibbering
authors.forename: Ernest K J
authors.initials: EK
authors.lastname: Pauwels
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000378:metabolism; D002177:Candidiasis / Q000000981:diagnostic imaging* / Q000378:metabolism; D003937:Diagnosis, Differential; D015725:Fluconazole / Q000493:pharmacokinetics; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging; D007781:Lactoferrin; D007970:Leukopenia / Q000000981:diagnostic imaging / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D009220:Myositis / Q000000981:diagnostic imaging* / Q000378:metabolism; D010446:Peptide Fragments / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D015203:Reproducibility of Results; D012269:Ribosomal Proteins / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D013667:Technetium / Q000493:pharmacokinetics; D013848:Thigh / Q000000981:diagnostic imaging / Q000503:physiopathology; D014018:Tissue Distribution
chemical_list: D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D012269:Ribosomal Proteins; C466658:lactoferrin (1-11), human; C040469:ribosomal protein S30; D013667:Technetium; D015725:Fluconazole; D007781:Lactoferrin