ngr-peptide and Myocardial-Infarction

As CD13 is selectively expressed in angiogenesis, it can serve as a target for molecular imaging tracers to noninvasively visualize angiogenic processes in vivo. The CD13-targeting moiety NGR was synthesized and cyclized by native chemical ligation (NCL) instead of disulfide bridging, leading to a cyclic peptide backbone: cyclo(Cys-Asn-Gly-Arg-Gly) (coNGR). Beside this new monomeric coNGR, a tetrameric NGR peptide co(NGR)

Topics: Animals; CD13 Antigens; Mice; Myocardial Infarction; Neovascularization, Pathologic; Oligopeptides; Tomography, Emission-Computed, Single-Photon

Peptides containing the asparagine-glycine-arginine (NGR) motif bind to aminopeptidase N (CD13), which is expressed on inflammatory cells, endothelial cells, and fibroblasts. It is unclear whether radiolabeled NGR-containing tracers could be used for in vivo imaging of the early wound-healing phase after myocardial infarction (MI) using positron emission tomography (PET).. Uptake of novel tracer [(68)Ga]NGR was assessed together with [(68)Ga]arginine-glycine-aspartic acid ([(68)Ga]RGD) and 2-deoxy-2-[(18) F]fluoro-D-glucose after myocardial ischemia/reperfusion (MI/R) injury using μ-PET and autoradiography, and relative expressions of CD13 and integrin β3 were assessed in fibroblasts, inflammatory cells, and endothelial cells by immunohistochemistry.. In the infarcted myocardium, uptake of [(68)Ga]NGR was maximal from days 3 to 7 after MI/R, and correlated with fibroblast and inflammatory cell infiltration as well as [(68)Ga]RGD uptake.. [(68)Ga]NGR allows noninvasive and sequential determination of CD13 expression in fibroblasts and inflammatory cells by PET. This will facilitate monitoring of CD13 in the individual wound healing processes, allowing patient-specific therapies to improve outcome after MI.

Topics: Amino Acid Motifs; Animals; CD13 Antigens; Fibroblasts; Gallium Radioisotopes; Heart; Humans; Immunohistochemistry; Inflammation; Male; Myocardial Infarction; Myocardial Ischemia; Myocardium; Oligopeptides; Positron-Emission Tomography; Rats; Rats, Wistar; Wound Healing

Angiogenesis is a natural mechanism to restore perfusion to the ischemic myocardium after acute myocardial infarction (MI). Therapeutic angiogenesis is being explored as a novel treatment for MI patients; however, sensitive, noninvasive in vivo measures of therapeutic efficacy are lacking and need to be developed. Here, a molecular magnetic resonance imaging method is presented to noninvasively image angiogenic activity in vivo in a murine model of MI with cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (pQDs). The tripeptide cNGR homes specifically to CD13, an aminopeptidase that is strongly upregulated during myocardial angiogenesis.. Acute MI was induced in male Swiss mice via permanent ligation of the left anterior descending coronary artery. Molecular magnetic resonance imaging was performed 7 days after surgery and up to 2 hours after intravenous contrast agent administration. Injection of cNGR-pQDs resulted in a strong negative contrast that was located mainly in the infarcted myocardium. This negative contrast was significantly less in MI mice injected with unlabeled pQDs and in sham-operated mice injected with cNGR-pQDs. Validation with ex vivo 2-photon laser scanning microscopy revealed a strong colocalization of cNGR-pQDs with vascular endothelial cells, whereas unlabeled pQDs were mostly extravasated and diffused through the tissue. Additionally, 2-photon laser scanning microscopy demonstrated significant microvascular remodeling in the infarct/border zones compared with remote myocardium.. cNGR-pQDs allow selective, noninvasive detection of angiogenic activity in the infarcted heart with the use of in vivo molecular magnetic resonance imaging and ex vivo 2-photon laser scanning microscopy.

Topics: Animals; CD13 Antigens; Contrast Media; Coronary Vessels; Disease Models, Animal; Ligation; Magnetic Resonance Imaging; Male; Mice; Microscopy, Confocal; Myocardial Infarction; Neovascularization, Physiologic; Oligopeptides; Ventricular Dysfunction, Left