Integrin αVβ3-targeted imaging of lung cancer

A series of radiolabeled cyclic arginine-glycine-aspartic acid (RGD) peptide ligands for cell adhesion molecule integrin alpha(v)beta(3)-targeted tumor angiogenesis targeting are being developed in our laboratory. In this study, this effort continues by applying a positron emitter Cu-64-labeled PEGylated dimeric RGD peptide radiotracer Cu-64-DOTA-PEG-E[c(RGDyK)](2) for lung cancer imaging. The PEGylated RGD peptide indicated integrin alpha(v)beta(3) avidity, but the PEGylation reduced the receptor binding affinity of this ligand compared to the unmodified RGD dimer. The radiotracer revealed rapid blood clearance and predominant renal clearance route. The minimum nonspecific activity accumulation in normal lung tissue and heart rendered high-quality orthotopic lung cancer tumor images, enabling clear demarcation of both the primary tumor at the upper lobe of the left lung, as well as metastases in the mediastinum, contralateral lung, and diaphragm. As a comparison, fluorodeoxyglucose (FDG) scans on the same mice were only able to identify the primary tumor, with the metastatic lesions masked by intense cardiac uptake and high lung background. Cu-64-DOTA-PEG-E[c(RGDyK)](2) is an excellent positron emission tomography (PET) tracer for integrin-positive tumor imaging. Further studies to improve the receptor binding affinity of the tracer and subsequently to increase the magnitude of tumor uptake without comprising the favorable in vivo kinetics are currently in progress.