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  • 1
    ISSN: 1619-7089
    Keywords: Radioiodination ; Interleukin-1 ; Infection ; Biodistribution ; Radionuclide imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, radioiodinated human recombinant interleukin-1 (IL-1) was investigated for its potential to image infectious foci in vivo in an animal model of infection. Twenty-four hours after induction of aStaphylococcus aureus abscess in the left calf muscle, mice were i.v. injected with both iodine-125 labelled IL-1 and iodine-131 labelled myoglobin, a size-matched control agent. The animals were killed for tissue biodistribution studies at 2, 6, 12, 24 and 48 h p.i. Gamma camera images were obtained at 6, 24 and 48 h after injecting mice with123I-IL-1. Radioiodinated IL-1 rapidly cleared from the body; after 12 h the abscess was the organ with the highest activity. The absolute abscess uptake of125I-IL-1 remained high compared to131I-myo-globin, resulting in significantly higher abscess-to-muscle ratios of125I-IL-1 compared to 1311-myoglobin. The ratios of125I-IL-1 reached the ultimate value of 44.4±10.8 at 48 h p.i., whereas the ratios of131I-myoglobin did not exceed 5.9±0.7. Gamma camera imaging revealed clearly visible abscesses. In conclusion, our results demonstrate specific retention of radioiodinated IL-1 in the abscess, presumably by interaction of IL-1 with its receptor on the inflammatory cells. The high target to-background ratios that were obtained over the course of time indicate that the IL-1 receptor may be a valuable target for the imaging of infectious foci.
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  • 2
    ISSN: 1619-7089
    Keywords: Radioiodination ; Interleukin-1 receptor antagonist ; Infection ; Biodistribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, we demonstrated that radiolabelled interleukin-lα (IL-1) specifically accumulates in focal infection in mice through interaction with its receptor. Unfortunately, systemic side-effects of IL-1 limit its clinical application. We investigated whether this problem could be circumvented by using the interleukin-1 receptor antagonist (IL-Ira), an equally sized protein that binds to the same receptors as IL-1 without induction of biological effects. Biodistribution of125I-IL-1 and125I-IL-Ira was determined in Swiss mice withStaphylococcus aureus-induced abscesses in the left calf muscle at 4, 12, 24 and 48 h after injection of either 0.4 MBq125I-IL1 or 0.4 MBq125I-IL-Ira. In vitro, the proteins displayed similar binding characteristics. High-performance liquid chromatographic analysis revealed a tendency for IL-Ira to associate with serum proteins. Both proteins rapidly cleared from most organs. However, the abscess uptake of125I-IL-Ira was significantly lower than that of125I-IL-1 at all time points (48 h p.i.: 0.06±0.01%ID/g vs 0.60±0.04%ID/g;P〈0.02). The abscess-to-contralateral muscle ratios did not exceed 15.5±2.9 for125I-IL-lra, while the ratios for125I-IL-1 reached 46.9±5.7 at 48 h p.i. Despite similar in vitro receptor binding, the abscess uptake of IL-Ira was much lower than that of IL-1. The interaction of IL-Ira with serum proteins in vivo may reduce its availability for receptor binding in the infection. Although on theoretical grounds IL-Ira is very interesting, these characteristics will prevent its development as a clinically useful radiopharmaceutical to image infection.
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