Title
A <tex>$^{99m}Tc$</tex>-labeled dual-domain cytokine ligand for imaging of inflammation A <tex>$^{99m}Tc$</tex>-labeled dual-domain cytokine ligand for imaging of inflammation
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Subject
Pharmacology. Therapy
Source (journal)
Nuclear medicine and biology
Volume/pages
38(2011) :6 , p. 795-805
ISSN
0969-8086
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
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 ischemicreperfused 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 ischemicreperfused 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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/f2537c/c8ae9b95757.pdf