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

11 Citations (Scopus)

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 2011

Fingerprint

Interleukins
Cytokines
Ligands
Inflammation
Ear
Interleukin-18
Competitive Binding
Interleukin-1
Neutrophils

Keywords

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

ASJC Scopus subject areas

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

Cite this

A 99mTc-labeled dual-domain cytokine ligand for imaging of inflammation. / Liu, Zhonglin; wyffels, Leonie; Barber, Christy; Hui, Mizhou M.; Woolfenden, James M.

In: Nuclear Medicine and Biology, Vol. 38, No. 6, 08.2011, p. 795-805.

Research output: Contribution to journalArticle

Liu, Zhonglin ; wyffels, Leonie ; Barber, Christy ; Hui, Mizhou M. ; Woolfenden, James M. / A 99mTc-labeled dual-domain cytokine ligand for imaging of inflammation. In: Nuclear Medicine and Biology. 2011 ; Vol. 38, No. 6. pp. 795-805.
@article{142af9b336e24357bb4092b75652a4ce,
title = "A 99mTc-labeled dual-domain cytokine ligand for imaging of inflammation",
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.",
keywords = "Tc, Inflammation, Interleukin-1, Interleukin-18, SPECT",
author = "Zhonglin Liu and Leonie wyffels and Christy Barber and Hui, {Mizhou M.} and Woolfenden, {James M.}",
year = "2011",
month = "8",
doi = "10.1016/j.nucmedbio.2011.02.012",
language = "English (US)",
volume = "38",
pages = "795--805",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - A 99mTc-labeled dual-domain cytokine ligand for imaging of inflammation

AU - Liu, Zhonglin

AU - wyffels, Leonie

AU - Barber, Christy

AU - Hui, Mizhou M.

AU - Woolfenden, James M.

PY - 2011/8

Y1 - 2011/8

N2 - 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.

AB - 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.

KW - Tc

KW - Inflammation

KW - Interleukin-1

KW - Interleukin-18

KW - SPECT

UR - http://www.scopus.com/inward/record.url?scp=80051678348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051678348&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2011.02.012

DO - 10.1016/j.nucmedbio.2011.02.012

M3 - Article

VL - 38

SP - 795

EP - 805

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 6

ER -