title: In vitro and in vivo evaluation of selected 68Ga-siderophores for infection imaging.
abstract: BACKGROUND
  Siderophores are low-molecular-mass iron chelators serving as iron transporters for almost all bacteria, fungi and some plants. Iron is an essential element for majority of organisms and plays an important role in virulence of pathogenic organisms. (68)Ga is a positron emitter with complexing properties comparable to those of Fe(III) and readily available from a generator. Initial studies with (68)Ga-triacetylfusarinine C (TAFC) showed excellent targeting properties in a rat infection model. We report here on the in vitro and in vivo evaluation of other siderophores radiolabelled with (68)Ga as potential radiopharmaceuticals for infection imaging.
  
  
  METHODS
  (68)Ga labelling was performed using acetate buffer. Stability, log P and protein binding values were determined. In vitro uptake was tested using iron-deficient and iron-sufficient Aspergillus fumigatus (A.f.) cultures. Biodistribution of (68)Ga-siderophores was studied in Balb/c mice.
  
  
  RESULTS
  Significant differences among studied siderophores were observed in labelling efficiency, stability and protein binding. Uptake in A.f. cultures was highly dependent on iron load and type of the siderophore. In mice, (68)Ga-TAFC and (68)Ga-ferrioxamine E (FOXE) showed rapid renal excretion and low blood values even at a short period after injection; in contrast, (68)Ga-ferricrocin and (68)Ga-ferrichrome revealed high retention in blood and (68)Ga-fusarinine C showed very high kidney retention.
  
  
  CONCLUSIONS
  Some of the studied siderophores bind (68)Ga with high affinity and stability, especially (68)Ga-TAFC and (68)Ga-FOXE. Low values of protein binding, high and specific uptake in A.f., and excellent in vivo biodistribution make them favourable agents for Aspergillus infection imaging.
authors.affiliation: Clinical Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Milos
authors.initials: M
authors.lastname: Petrik
authors.forename: Hubertus
authors.initials: H
authors.lastname: Haas
authors.forename: Markus
authors.initials: M
authors.lastname: Schrettl
authors.forename: Anna
authors.initials: A
authors.lastname: Helbok
authors.forename: Michael
authors.initials: M
authors.lastname: Blatzer
authors.forename: Clemens
authors.initials: C
authors.lastname: Decristoforo
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000000981:diagnostic imaging* / Q000382:microbiology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000378:metabolism*; D001667:Binding, Competitive; D005290:Ferric Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006877:Hydroxamic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D017262:Siderophores / Q000737:chemistry* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; D005710:Gallium Radioisotopes; D006877:Hydroxamic Acids; D010456:Peptides, Cyclic; D017262:Siderophores; C017508:ferrioxamine E; C053324:N,N',N''-triacetylfusarinine C