Detection of Antecedent Myocardial Ischemia With Multiselectin Molecular Imaging

Abstract

Objective Our aim was to develop an echocardiographic molecular imaging approach for detecting recent myocardial ischemia by using recombinant P-selectin glycoprotein ligand (PSGL)-1 as a targeting ligand, which is a feasible approach for human use. Background Ischemic memory imaging using human PSGL-1 as a targeting moiety may extend the time window for postischemic detection by targeting the early (P-selectin) and late (E-selectin) endothelial ischemic response. Methods Lipid microbubbles bearing recombinant human PSGL-1 (MBYSPSL) or P-selectin antibody (MBAb) were prepared. Targeted attachment was evaluated by using flow chamber and intravital microscopy. In vivo ultrasound molecular imaging was first performed in the hindlimb in wild-type and P-selectin–deficient (P−/−) mice 45 to 360 min after brief ischemia-reperfusion injury. Myocardial contrast echocardiography molecular imaging was performed 1.5, 3, 6, and 18 h after brief left anterior descending coronary artery ischemia-reperfusion. Results Microbubble attachment to P-selectin–immunoglobulin G fusion protein in flow chamber experiments (shear stress 0.5 to 8.0 dyne/cm2) and to activated venular endothelium on intravital microscopy were similar for MBAb and MBYSPSL. Intense enhancement was seen for MBAb and MBYSPSL in postischemic muscle and was more stable over time for MBYSPSL. On myocardial contrast echocardiography, both MBYSPSL and MBAb produced similar signal enhancement at 90 min and 3 h after ischemia, which spatially correlated with the postischemic risk area. Signal significantly decreased but was still present at 6 to 18 h. Conclusions Echocardiographic molecular imaging with a human multi-selectin–targeted contrast agent bearing recombinant human PSGL-1 can detect myocardial ischemia hours after resolution. This approach may potentially be used for rapid bedside evaluation of patients with recent chest pain.

Noninvasive Molecular Ultrasound Monitoring of Vessel Healing After Intravascular Surgical Procedures in a Preclinical Setup

“…This was recently demonstrated with clinically applicable poly-n-butylcyanoacrylate MBs based on a peptide ligand for specific imaging of E-selectin expression in tumor blood vessels, 39 as well as with angiogenesis-specific VEGFR 2 -MBs in molecular imaging of breast and prostate cancer, 40,41 and with P-and E-selectin-targeted MBs in inflammatory bowel disease 42 and myocardial infarction. 43 Following these examples of clinically translatable molecular ultrasound contrast agents, the generation of a MB VCAM-1 with covalently attached targeting ligands would be a logical and practicable next step for future clinical implementation. Moreover, metal stents are not suitable for ultrasound imaging because the acoustic reflectivity of the stent would obstruct MB detection and impede healing assessments.…”

Molecular Imaging of Inflammation in Inflammatory Bowel Disease with a Clinically Translatable Dual-Selectin–targeted US Contrast Agent: Comparison with FDG PET/CT in a Mouse Model

“…US imaging with MB Selectin correlates well with FDG uptake at PET/CT imaging. (11), it is an attractive binding ligand with which to develop a clinically translatable molecularly targeted contrast agent for US imaging of inflammation, thereby leveraging the natural pathway of leukocyte recruitment in inflammatory tissue as a biomarker of inflammation (12,13). The purpose of this study was to develop and test a molecular imaging approach that uses US and a recently develped clinically translatable dualtargeted (P-and E-selectin) contrast agent (MB Selectin ) in the quantification of inflammation at the molecular level and to quantitatively correlate selectintargeted US with fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and computed tomography (CT) in terms of visualization and quantification of different levels of inflammation in a murine acute colitis model.…”

Clinical effect of intravenous thrombolysis combined with nicorandil therapy in patients with acute ST-segment elevation myocardial infarction

“…Like patients with general acute MI, patients who develop STEMI also have symptoms of chest pain and arrhythmia; but the most representative characteristic is a significant elevation of STsegment on the electrocardiogram [1]. The incidence of STEMI has become increasingly high of recent, seriously threatening people's health.…”