Cu-1,4,7,10-Tetraazacyclododecane-,,,-tetraacetic acid -cyclic arginine-glycine-aspartic acid peptide [Cu-DOTA-c(RGDyK)] is an integrin-targeted molecular imaging agent developed for positron emission tomography (PET) of tumor vasculature, tumor angiogenesis, and osteoclasts (1). Cellular survival, invasion, and migration control embryonic development, angiogenesis, tumor metastasis, and other physiologic processes (2, 3). Among the molecules that regulate angiogenesis are integrins, which comprise a superfamily of cell adhesion proteins that form heterodimeric receptors for extracellular matrix (ECM) molecules (4, 5). These transmembrane glycoproteins consist of two noncovalently associated subunits, α and β (18 α- and 8 β-subunits in mammals), which are assembled into at least 24 α/β pairs. Several integrins, such as integrin αβ, have affinity for the arginine-glycine-aspartic acid (RGD) tripeptide motif, which is found in many ECM proteins. Expression of integrin αβ receptors on endothelial cells is stimulated by angiogenic factors and environments. The integrin αβ receptor is generally not found in normal tissue, but it is strongly expressed in vessels with increased angiogenesis, such as tumor vasculature. It is significantly upregulated in certain types of tumor cells and in almost all tumor vasculature. Molecular imaging probes carrying the RGD motif that binds to the integrin αβ can be used to image tumor vasculature and evaluate angiogenic response to tumor therapy (6, 7). Various RGD peptides in both linear and cyclic forms have been developed for binding to integrin αβ (8). Chen et al. (1) evaluated a cyclic RGD peptide [c(RGDyK)] labeled with Cu or F in nude mice bearing breast tumor. They used DOTA for c(RGDyK) conjugation with Cu. Cu-DOTA-c(RGDyK) showed prolonged tumor radioactivity retention but persistent liver radioactivity.