THE KINETICS OF RADIOLABELED INTERLEUKIN-8 IN INFECTION AND STERILE INFLAMMATION

Radiolabelled interleukin-8 (IL-8) is a promising agent for the imagin g 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 infec tion (Escherichia coli, Staphylococcus aureus) or sterile inflammation (zymosan) were injected intravenously with 18.5 MBq (0.5 mCi) of I-12 3-IL-8. In separate studies, rabbits were injected intravenously with In-111-granulocytes with or without I-125-IL-8. Gamma camera images we re obtained at 5 min, 1, 4 and 8 h post-injection (p.i.). Biodistribut ion was determined at 8 h p.i. In all models, the biodistribution of I -123-IL-8 was characterized by rapid blood clearance and high uptake i n infection and sterile inflammation. All foci could be clearly visual ized within 4 h p.i. Ex vivo abscess-to-contralateral muscle ratios in creased 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 I-123-IL-8 wa s bound to erythrocytes. The abscess uptake of I-125-IL-8 reached high levels despite reduced migration of granulocytes towards the site of infection due to the anti-inflammatory activity of intravenously injec ted IL-8. IL-8 could be injected without induction of neutropenia at a dosage of 2 ng kg-1. In conclusion, the characteristics of radiolabel led IL-8 for imaging of infection and sterile inflammation are highly encouraging and warrant further optimization for clinical application. ((C) 1998 Chapman & Hall Ltd.).