title: The kinetics of radiolabelled interleukin-8 in infection and sterile inflammation.
abstract: Radiolabelled interleukin-8 (IL-8) is a promising agent for the imaging of infection and inflammation. Several experiments were performed to explore further the imaging potential of radiolabelled IL-8. IL-8 was radioiodinated via the Bolton-Hunter method. Rabbits with focal infection (Escherichia coli, Staphylococcus aureus) or sterile inflammation (zymosan) were injected intravenously with 18.5 MBq (0.5 mCi) of 123I-IL-8. In separate studies, rabbits were injected intravenously with 111In-granulocytes with or without 125I-IL-8. Gamma camera images were obtained at 5 min, 1, 4 and 8 h post-injection (p.i.). Biodistribution was determined at 8 h p.i. In all models, the biodistribution of 123I-IL-8 was characterized by rapid blood clearance and high uptake in infection and sterile inflammation. All foci could be clearly visualized within 4 h p.i. Ex vivo abscess-to-contralateral muscle ratios increased to 114.7+/-23.0 (E. coli), 52.3+/-24.5 (S. aureus) and 49.8+/-8.3 (zymosan) at 8 h p.i. In the circulation, most 123I-IL-8 was bound to erythrocytes. The abscess uptake of 125I-IL-8 reached high levels despite reduced migration of granulocytes towards the site of infection due to the anti-inflammatory activity of intravenously injected IL-8. IL-8 could be injected without induction of neutropenia at a dosage of 2 ng kg(-1). In conclusion, the characteristics of radiolabelled IL-8 for imaging of infection and sterile inflammation are highly encouraging and warrant further optimization for clinical application.
authors.affiliation: Department of Nuclear Medicine, University Hospital 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: Ven der Meer
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000097:blood; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000276:immunology*; D016209:Interleukin-8 / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018123:Receptors, Interleukin / Q000097:blood; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging / Q000276:immunology*; D013211:Staphylococcus aureus; D014018:Tissue Distribution; D015054:Zymosan
chemical_list: D015703:Antigens, CD; D016209:Interleukin-8; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; D015054:Zymosan