A (99m)Tc-labeled dual-domain cytokine ligand for imaging of inflammation

作者：Liu Zhonglin^*; Wyffels Leonie; Barber Christy; Hui Mizhou M; Woolfenden James M

来源：Nuclear Medicine and Biology, 2011, 38(6): 795-805.

DOI：10.1016/j.nucmedbio.2011.02.012

• (99m)Tc
• Interleukin-1
• Interleukin-18
• Inflammation
• SPECT

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 (99m)Tc-radiolabel an IL-1ra and IL-18bp dual-domain cytokine ligand, IL-18bp-Fc-IL-1ra, for specific inflammation targeting.
Methods: The (99m)Tc-IL-18bp-Fc-IL-1ra was obtained by direct labeling via 2-iminothiolane reduction. Competitive binding of (99m)Tc-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 (99m)Tc-IL-18bp-Fc-IL-1ra in vivo. The correlation between (99m)Tc-IL-18bp-Fc-IL-1ra uptake and (III)In-labeled polymorphonuclear neutrophil infiltration was studied using ischemic reperfused rat hearts.
Results: Direct (99m)Tc-labeling yielded a stable dual-domain cytokine radioligand with radiochemical purity greater than 95% after gel filtration. Competitive binding studies showed specific targeting of (99m)Tc-IL-18bp-Fc-IL-1ra to inflammatory cells. The (99m)Tc-IL-18bp-FcIL-1ra uptake was 1.80 +/- 0.17% injected dose per gram (Wig) 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-1 beta and IL-18 were significantly increased in the inflamed ears compared to the vehicle controls. A significant correlation of (99m)Tc-IL-18bp-Fc-IL-1ra with (III)min-labeled neutrophil distribution was observed in the ischemic reperfused hearts (P<.001).
Conclusion: Targeting proinflammatory cytokines with (99m)Tc-IL-18bp-Fc-IL-1ra may provide a suitable approach for specific detection of inflammatory sites.

• 出版日期2011-8