PT - JOURNAL ARTICLE AU - Zhonglin Liu AU - Christy Barber AU - Li Wan AU - Shan Liu AU - Mizhou M. Hui AU - Lars R. Furenlid AU - Hua Xu AU - James M. Woolfenden TI - SPECT Imaging of Inflammatory Response in Ischemic–Reperfused Rat Hearts Using a <sup>99m</sup>Tc-Labeled Dual-Domain Cytokine Ligand AID - 10.2967/jnumed.113.123497 DP - 2013 Dec 01 TA - Journal of Nuclear Medicine PG - 2139--2145 VI - 54 IP - 12 4099 - http://jnm.snmjournals.org/content/54/12/2139.short 4100 - http://jnm.snmjournals.org/content/54/12/2139.full SO - J Nucl Med2013 Dec 01; 54 AB - 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 99mTc-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, 99mTc-IL-1ra-Fc (IF) and 99mTc-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 &lt; 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.