28) Yan et al.29) evaluated the ability of molecular ultrasound to detect the presence of ICAM-1, which is upregulated on the venular endothelial surface later than P-selectin, but persists for much longer – with peak expression at 24 h after reperfusion. Accordingly, biotinylated microbubbles conjugated with a monoclonal antibody targeted against www.selleckchem.com/products/tariquidar.html ICAM-1 were administered at 1, 8 and 24 h after a brief 15 min ischemic insult in mice. Selective enhancement of the post-ischemic anterior myocardium was demonstrated at the 8 and 24 h time points using targeted Inhibitors,research,lifescience,medical microbubbles. At 1 h, though, anti-ICAM-1 targeted microbubbles did not cause greater enhancement than microbubbles
Inhibitors,research,lifescience,medical conjugated with a control antibody.29) These experiments demonstrate the dramatic ability of targeted imaging
to identify myocardium which has been ischemic even up to 24 h after the insult. The endothelial target of choice will vary depending on the interval between the ischemic insult and the time of imaging (P-selectin early and ICAM-1 late), which highlights the need for a user to have good understanding of molecular biology to take full advantage of this technology. Fig. 4 Background-subtracted, color-coded images of microbubbles targeted to P-selectin enhancing the perfusion bed of the left anterior descending coronary artery (A), and the left circumflex Inhibitors,research,lifescience,medical coronary artery (B). Images were obtained 60 min after reperfusion … Another condition characterized Inhibitors,research,lifescience,medical by inflammation is acute heart transplant rejection. Rats that had undergone heterotopic cardiac transplantation with and without acute rejection were administered microbubbles targeted to ICAM-1. Inhibitors,research,lifescience,medical Persistent diffuse myocardial contrast enhancement was noted in rejecting allografts after administration of targeted microbubbles, while no enhancement was seen after administration of control microbubbles.30) Detection of early atherosclerosis Atheromatous lesions are sites of endothelial dysfunction,
intimal thickening, and there is overexpression of adhesion molecules to mediate leukocyte infiltration into plaque.31) The ability to detect early atherosclerosis in vivo, prior to the development of a significantly stenotic lesion or a cardiovascular event, aminophylline could potentially be used to identify high risk individuals in need of aggressive treatment and risk-factor modification for primary prevention. The ability of microbubbles labeled with vascular cell adhesion molecule-1 (VCAM-1) to identify early atherosclerotic lesions in the aorta of apo-E knockout mouse has now been demonstrated.32) The degree of contrast enhancement was related to the extent of plaque, so targeted microbubbles can not only detect the presence of early atheromatous lesions, but also quantify the degree of associated inflammation.