title: Imaging of infection in rabbits with radioiodinated interleukin-1 (alpha and beta), its receptor antagonist and a chemotactic peptide: a comparative study.
abstract: Previous studies have reported the favourable characteristics of chemotactic peptides and interleukins for imaging of infection and inflammation. In the present study, the potential of two species of interleukin 1 (IL-1), IL-1alpha and IL-1beta, the IL-1 receptor antagonist (IL-1ra) and the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanyl-lysine (fMLFK) were directly compared in a rabbit model of infection. IL-1alpha, IL-1beta, IL-1ra and fMLFK were labelled with iodine-123 according to the Bolton-Hunter method. Twenty-four hours after induction of Escherichia coli abscesses in the left thigh muscle, rabbits were injected intravenously with 0.5 mCi of 123I-labelled agent. Gamma camera images were obtained at 5 min and 1, 4, 8 and 20 h p.i. Biodistribution was determined at 20 h p.i. Although all agents rapidly cleared from the blood, at 20 h p.i. blood levels and the levels in most organs of 123I-fMLFK were significantly lower than those of the other three agents (P<0.05). The abscesses were clearly visualized with all agents from 4 h p.i. onwards. After 1 h p.i., the abscess uptake of 123I-IL-1beta was significantly higher than that of the other agents (P<0.05), with the highest uptake observed at 8 h p.i. (1.3%+/-0.3%). After 20 h p.i., the highest abscess-to-contralateral muscle ratios were obtained with 123I-IL-1beta, i.e. 39.0+/-11.5 vs 18.7+/-5.4, 18.1+/-2.3 and 29. 9+/-7.0 for 123I-IL-1alpha, 123I-IL-1ra and 123I-fMLFK, respectively. In conclusion, all agents localized in the infectious focus. The potential of radiolabelled IL-1beta for imaging of infection was better than that of the other agents: higher absolute uptake in the infection and higher abscess-to-contralateral muscle ratios were obtained. The observation of localization of radiolabelled IL-1ra in infection was important since this protein can be administered to humans without any side-effects.
authors.affiliation: Department of Nuclear Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: van der Laken
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: M T
authors.initials: MT
authors.lastname: van de Ven
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
mesh_terms: D000038:Abscess / Q000000981:diagnostic imaging*; D000818:Animals; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging*; D005260:Female; D006614:Hindlimb; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011817:Rabbits; D011877:Radionuclide Imaging; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution
chemical_list: D007375:Interleukin-1; D007457:Iodine Radioisotopes; D018123:Receptors, Interleukin; D009240:N-Formylmethionine Leucyl-Phenylalanine