A 99mTc-labeled dual-domain cytokine ligand for imaging of inflammation

Zhonglin Liu, Leonie wyffels, Christy Barber, Mizhou M. Hui, James M. Woolfenden

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Introduction: Interleukin (IL)-1 and IL-18 are potent proinflammatory cytokines in inflammation-related diseases. Their actions are regulated by IL-1 receptor antagonist (IL-1ra) and IL-18 binding protein (IL-18bp). This study was designed to 99mTc-radiolabel an IL-1ra and IL-18bp dual-domain cytokine ligand, IL-18bp-Fc-IL-1ra, for specific inflammation targeting. Methods: The 99mTc-IL-18bp-Fc-IL-1ra was obtained by direct labeling via 2-iminothiolane reduction. Competitive binding of 99mTc-labeled and unlabeled IL-18bp-Fc-IL-1ra to rat polymorphonuclear leukocytes was assessed in vitro. A mouse ear edema model was used to evaluate specific targeting properties of 99mTc-IL-18bp-Fc-IL1ra in vivo. The correlation between 99mTc-IL-18bp-Fc-IL-1ra uptake and 111In-labeled polymorphonuclear neutrophil infiltration was studied using ischemic-reperfused rat hearts. Results: Direct 99mTc-labeling yielded a stable dual-domain cytokine radioligand with radiochemical purity greater than 95% after gel filtration. Competitive binding studies showed specific targeting of 99mTc-IL-18bp-Fc-IL-1ra to inflammatory cells. The 99mTc-IL-18bp-Fc-IL-1ra uptake was 1.80±0.17 % injected dose per gram (%ID/g) in the inflamed ear without blocking, whereas uptake in the presence of IL-18bp-Fc-IL-1ra was 1.09±0.08 %ID/g (P<05). The amounts of IL-1β and IL-18 were significantly increased in the inflamed ears compared to the vehicle controls. A significant correlation of 99mTc-IL-18bp-Fc-IL-1ra with 111In-labeled neutrophil distribution was observed in the ischemic-reperfused hearts (P<001). Conclusion: Targeting proinflammatory cytokines with 99mTc-IL-18bp-Fc-IL-1ra may provide a suitable approach for specific detection of inflammatory sites.

Original languageEnglish (US)
Pages (from-to)795-805
Number of pages11
JournalNuclear Medicine and Biology
Volume38
Issue number6
DOIs
StatePublished - Aug 1 2011

    Fingerprint

Keywords

  • Inflammation
  • Interleukin-1
  • Interleukin-18
  • SPECT
  • Tc

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this