Details

Autor(en) / Beteiligte

• Ye, Fei
• Fang, Wei
• Wang, Feng
• Hua, Zi-Chun
• Wang, Zizheng
• Yang, Xiang

Titel

Evaluation of adenosine preconditioning with99m Tc-His10 -annexin V in a porcine model of myocardium ischemia and reperfusion injury: preliminary study

Ist Teil von

• Nuclear medicine and biology, 2011, Vol.38 (4), p.567-574

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Purpose The goal of this study was to evaluate the feasibility of99m Tc-His10 -annexin V for the detection of acute myocardial cell death and to assess the effect of adenosine preconditioning in a porcine model of myocardium ischemia and reperfusion injury (RI). Materials and Methods99m Tc-His10 -annexin V was prepared by one-step direct labeling, and RCP and radiostability were tested. The binding of99m Tc-His10 -annexin V to apoptosis was validated in vitro using camptothecin-induced Jurkat cells. In vivo biodistribution was determined in mice by the dissection method. Ischemia of 20–30 min was induced by balloon occlusion of the epicardial coronary artery of the porcine model ( n =14). Adenosine was infused intravenously in six pigs before coronary occlusion.99m Tc-His10 -annexin V ( n =12) was injected intravenously at 1 h after reperfusion. SPECT/CT was acquired at 3 h postinjection. Myocardial perfusion imaging (MPI) with99m Tc-MIBI was also performed 1 day after His10 -annexin V imaging. Cardiac tissues were analyzed postmortem using hematoxylin-and-eosin and TUNEL staining. Caspase-3 activity was measured to confirm the presence of apoptosis. Results99m Tc-His10 -annexin V had a RCP >98% and high stability 2 h after radiolabeling; it could bind to apoptotic cells with high affinity. Biodistribution of99m Tc-His10 -annexin V showed a predominant uptake in the kidney and relatively low uptake in the myocardium, liver and gastrointestinal tract; rapid clearance from blood and kidney was observed. In the untreated group, intense uptake of His10 -annexin V was visualized in the defect which was shown in MPI, whereas in the adenosine group a mild uptake of99m Tc-His10 -annexin was found in the risk area which showed no defects in the99m Tc-MIBI image. TUNEL staining and activated caspase-3 confirmed the ongoing apoptosis in RI. Adenosine preconditioning significantly diminished the level of apoptosis. Uptake of His10 -annexin V in RI correlated with TUNEL-positive nuclei. Conclusion This study addresses the feasibility of imaging of myocardial cell death in acute ischemia and RI in pigs with99m Tc-His10 -annexin V; it holds prospect for the detection of myocardial cell death in clinical practice. Adenosine preconditioning could attenuate the myocardial apoptosis; its cardioprotective effect might partially be fulfilled by suppressing the ongoing apoptosis in ischemia and reperfusion. Further study is warranted.