Abstract
Background: A major impediment to drug diagnosis and therapy of myocardial infarction is the limited access that drugs have to ischemic myocardium, dependent on regional myocardial blood flow. Investigators report that some liposomes concentrate in the experimental myocardial infarction, suggesting that they may be used to transport drugs to a region of ischemia. One of the most promising approaches for increasing liposome circulation time is coating them with polyethyleneglycol (PEG). Methodology: Unilamellar PEG-coated neutrally charged and positive non-PEG liposomes, both labelled with 99mTc, were produced. A rabbit myocardial ischemia-reperfusion model was created in which a silk ligature was reversibly tied around the left anterior descending coronary artery (LAD). After 90 minutes of ischemia LAD ligature was untied, 99mTc-liposomes were injected in the rabbit model, and we followed their distribution during the next 3 hours with gamma camera imaging (dynamic, static and spet acquisitions). 201Tl was simultaneously injected and we also followed its distribution/redistribution through the next 3 hours. After in vivo cyntigraphic study, the isolated heart was placed on the gamma camera so a static and a spet acquisition could be made. Tissue samples were obtained from the 3 myocardial regions (nonischemic, viable and infarcted) as well as from other organs of interest for biodistribution study following a standard scheme. Results/conclusions: A functional and reproductible rabbit myocardial ischemia-reperfusion model was successfully created. Neutral PEG-coated liposomes have higher in vitro and in vivo stability than positive non-PEG. On in vivo images, 201TI redistribution areas which correspond to viable myocardium match the areas of higher 99mTc-liposome concentration either neutral-PEG and positive non-PEG. Biodistribution study confirmed important cardiac radioactivity with higher relative values in ischemic myocardium than in normal myocardium.
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