title: SPECT imaging of myocardial infarction using 99mTc-labeled C2A domain of synaptotagmin I in a porcine ischemia-reperfusion model.
abstract: BACKGROUND
  The C2A domain of synaptotagmin I recognizes necrotic and apoptotic cells by binding to exposed anionic phospholipids. The goal is to explore the potential imaging utility of 99mTc-labeled C2A in the detection of acute cardiac cell death in a porcine model that resembles human cardiovascular physiology.
  
  
  METHODS
  Ischemia (20-25 min) was induced in pigs (M/F, 20-25 kg) using balloon angioplasty. 99mTc-C2A-GST (n=7) or 99mTc-BSA (n=2) was injected intravenously 1-2 h after reperfusion. Noninfarct animals were injected with 99mTc-C2A-GST (n=4). SPECT images were acquired at 3 and 6 h postinjection. Cardiac tissues were analyzed to confirm the presence of cell death.
  
  
  RESULTS
  Focal uptake was detected in five out of seven subjects at 3 h and in all infarct subjects at 6 h postinjection but not in infarct animals injected with 99mTc-BSA or in noninfarct animals with 99mTc-C2A-GST. Gamma counting of infarct versus normal myocardium yielded a 10.2+/-5.7-fold elevation in absolute radioactivity, with histologically confirmed infarction.
  
  
  CONCLUSIONS
  We present data on imaging myocardial cell death in the acute phase of infarction in pigs. C2A holds promise and warrants further development as an infarct-avid molecular probe.
authors.affiliation: Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Shundong
authors.initials: S
authors.lastname: Ji
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Zhu
authors.forename: Heidi T
authors.initials: HT
authors.lastname: Meier
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hellman
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
authors.forename: Bazbek
authors.initials: B
authors.lastname: Davletov
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis; D003198:Computer Simulation; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008657:Metabolic Clearance Rate; D008955:Models, Cardiovascular; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*; D013552:Swine; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; C526993:technetium 99m C2A-glutathione transferase