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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 Publication | JOURNAL OF NUCLEAR MEDICINE
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Volume | 54Issue:12Pages:2139-2145 |
Abstract | 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. |
Keyword | Interleukin-1 Tumor Necrosis Factor Inflammation Tc-99m Myocardial Ischemia-reperfusion |
Subtype | Article |
WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
Indexed By | SCI |
Language | 英语 |
WOS Keyword | INTERLEUKIN-1 RECEPTOR ANTAGONIST ; ACUTE MYOCARDIAL-INFARCTION ; NECROSIS-FACTOR-ALPHA ; TNF-ALPHA ; CARDIAC DYSFUNCTION ; MESSENGER-RNA ; IN-VIVO ; EXPRESSION ; INFECTION ; ACTIVATION |
WOS Research Area | Radiology, Nuclear Medicine & Medical Imaging |
WOS Subject | Radiology, Nuclear Medicine & Medical Imaging |
WOS ID | WOS:000328013000019 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ipe.ac.cn/handle/122111/13475 |
Collection | 研究所(批量导入) |
Affiliation | 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 |
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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SPECT Imaging of Inf(1066KB) | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | Application Full Text |
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