SPECT imaging of inflammatory response in ischemic-reperfused rat hearts using a 99mTc-labeled dual-domain cytokine ligand

Zhonglin Liu, Christy Barber, Li Wan, Shan Liu, Mizhou M. Hui, Lars R. Furenlid, Hua Xu, James M. Woolfenden

Research output: Contribution to journalArticle

4 Scopus citations

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 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 versusmicrosphere-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 5 ± 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. COPYRIGHT

Original languageEnglish (US)
Pages (from-to)2139-2145
Number of pages7
JournalJournal of Nuclear Medicine
Volume54
Issue number12
DOIs
StatePublished - Dec 1 2013

Keywords

  • Inflammation
  • Interleukin-1
  • Myocardial ischemia-reperfusion
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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