Extracellular matrix (ECM) adhesion molecules consist of a complex network of fibronectins, collagens, chondroitins, laminins, glycoproteins, heparin sulfate, tenascins, and proteoglycans that surround connective tissue cells, and they are mainly secreted by fibroblasts, chondroblasts, and osteoblasts (1). Cell substrate adhesion molecules are considered essential regulators of cell migration, differentiation, and tissue integrity and remodeling. These molecules play a role in inflammation and atherogenesis, but they also participate in the process of invasion and metastasis of malignant cells in the host tissue (2). Fibrosis is the formation of excess fibrous connective tissue (mainly collagen type I) in an organ or tissue as a reparative or reactive process in many chronic diseases in the heart, liver, kidneys, lungs, or vasculature.
Tumor angiogenesis represents a continuous and important process in tumor development in which the tumor attempts to gain an independent blood supply (3). This process is driven by the tumor's overproduction of angiogenic factors, which bind to receptors on nearby vessel endothelial cells. Angiogenesis is essential for the growth of solid tumors and their metastases. Imaging angiogenesis may be useful for monitoring angiogenic treatments of tumors and cardiovascular diseases (4-6). Aminopeptidase N (APN, CD13) is a membrane bound glycoprotein with MMP activity that cleaves unsubstituted, N-terminal amino acids with neutral side chains from peptides (7). APN has been shown to play a role in tumor angiogenesis, invasion, and metastasis (8). In addition to endothelial cells of angiogenic vessels, most cells of myeloid origin, epithelial cells, fibroblasts and smooth muscle cells also express CD13 (9, 10). The tumor homing peptide cyclo(Cys-Asn-Gly-Arg-Cys)-Gly-Lys (cNGR) contains the Asn-Gly-Arg (NGR) motif that binds to APN (11). Buehler et al. (12) has conjugated cNGR with Oregon Green 488 (OG488) to study angiogenesis in a murine myocardial infarction model.