SPECT Imaging of Inflammatory Response in Ischemic-Reperfused Rat Hearts Using a Tc-99m-Labeled Dual-Domain Cytokine Ligand

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	SPECT Imaging of Inflammatory Response in Ischemic-Reperfused Rat Hearts Using a Tc-99m-Labeled Dual-Domain Cytokine Ligand
	Liu, Zhonglin 1; Barber, Christy 1; Wan, Li 1; Liu, Shan 2; Hui, Mizhou M.2,3; Furenlid, Lars R.1; Xu, Hua 4; Woolfenden, James M.1
刊名	JOURNAL OF NUCLEAR MEDICINE
	2013-12-01
卷号	54 期号:12 页码:2139-2145
关键词	interleukin-1 tumor necrosis factor inflammation Tc-99m myocardial ischemia-reperfusion
英文摘要	Soluble 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.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Radiology, Nuclear Medicine & Medical Imaging
研究领域[WOS]	Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]	INTERLEUKIN-1 RECEPTOR ANTAGONIST ; ACUTE MYOCARDIAL-INFARCTION ; NECROSIS-FACTOR-ALPHA ; TNF-ALPHA ; CARDIAC DYSFUNCTION ; MESSENGER-RNA ; IN-VIVO ; EXPRESSION ; INFECTION ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000328013000019
公开日期	2015-05-27
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/13475]
专题	过程工程研究所_研究所（批量导入）
作者单位	1.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
推荐引用方式 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.