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SPECT Imaging of Inflammatory Response in Ischemic-Reperfused Rat Hearts Using a Tc-99m-Labeled Dual-Domain Cytokine Ligand
Liu, Zhonglin1; Barber, Christy1; Wan, Li1; Liu, Shan2; Hui, Mizhou M.2,3; Furenlid, Lars R.1; Xu, Hua4; Woolfenden, James M.1
2013-12-01
Source PublicationJOURNAL OF NUCLEAR MEDICINE
Volume54Issue:12Pages:2139-2145
AbstractSoluble tumor necrosis factor (TNF) receptor-2 (TNFR2) and interleukin-1 receptor antagonist (IL-1ra) were fused to the Fc portion of IgG1 using recombinant DNA technology. The resulting dual-domain cytokine ligand, TNFR2-Fc-IL-1ra, specifically binds to TNF and to the type I IL-1 receptor (IL-1RI). This study was designed to characterize the kinetic profile of Tc-99m-labeled TNFR2-Fc-IL-1ra (TFI) for imaging inflammatory response in an ischemic-reperfused (IR) rat heart model. Methods: The IR model was created by ligating the left coronary artery for 45 min, followed by 2-h reperfusion. Cardiac SPECT images of TFI in the IR model (n = 6) were dynamically acquired for 3 h. Correlative data of myocardial TFI distribution versus microsphere-determined tissue blood flow were acquired in 3 extra IR hearts. Inflammation targeting affinity of TFI was compared with 2 individual cytokine radioligands, Tc-99m-IL-1ra-Fc (IF) and Tc-99m-TNFR2-Fc (TF) (n = 6 each group). Myocardial cytokine expression was evaluated by immunochemical assay. Results; Increased TFI uptake was found in the ischemic area and correlated with the severity of ischemia. At 3 h after injection, the ratio of hot-spot accumulation in the ischemic area to a remote viable zone was 5.39 +/- 1.11 for TFI, which was greater than that for IF (3.28 +/- 0.81) and TF (3.29 +/- 0.75) (P < 0.05). The in vivo uptake profiles of TFI, TF, and IF were consistent with ex vivo radioactive measurements and correlated with upregulated IL-1 and TNF expression. Conclusion: The dual-domain TFI is promising for noninvasive detection of inflammatory reactions in IR myocardium because of its more potent affinity to the inflammatory sites compared with TF and IF.
KeywordInterleukin-1 Tumor Necrosis Factor Inflammation Tc-99m Myocardial Ischemia-reperfusion
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS KeywordINTERLEUKIN-1 RECEPTOR ANTAGONIST ; ACUTE MYOCARDIAL-INFARCTION ; NECROSIS-FACTOR-ALPHA ; TNF-ALPHA ; CARDIAC DYSFUNCTION ; MESSENGER-RNA ; IN-VIVO ; EXPRESSION ; INFECTION ; ACTIVATION
WOS Research AreaRadiology, Nuclear Medicine & Medical Imaging
WOS SubjectRadiology, Nuclear Medicine & Medical Imaging
WOS IDWOS:000328013000019
Citation statistics
Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/13475
Collection研究所(批量导入)
Affiliation1.Univ Arizona, Dept Med Imaging, Tucson, AZ 85724 USA
2.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing, Peoples R China
3.AmProt Corp, San Gabriel, CA USA
4.Univ Arizona, Dept Pediat, Tucson, AZ 85724 USA
Recommended Citation
GB/T 7714
Liu, Zhonglin,Barber, Christy,Wan, Li,et al. SPECT Imaging of Inflammatory Response in Ischemic-Reperfused Rat Hearts Using a Tc-99m-Labeled Dual-Domain Cytokine Ligand[J]. JOURNAL OF NUCLEAR MEDICINE,2013,54(12):2139-2145.
APA Liu, Zhonglin.,Barber, Christy.,Wan, Li.,Liu, Shan.,Hui, Mizhou M..,...&Woolfenden, James M..(2013).SPECT Imaging of Inflammatory Response in Ischemic-Reperfused Rat Hearts Using a Tc-99m-Labeled Dual-Domain Cytokine Ligand.JOURNAL OF NUCLEAR MEDICINE,54(12),2139-2145.
MLA Liu, Zhonglin,et al."SPECT Imaging of Inflammatory Response in Ischemic-Reperfused Rat Hearts Using a Tc-99m-Labeled Dual-Domain Cytokine Ligand".JOURNAL OF NUCLEAR MEDICINE 54.12(2013):2139-2145.
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