A peptide-targeted MRI contrast agent for cancer molecular imaging

Introduction: Early detection and diagnosis of malignant tumors enable more efficacious cancer treatment at an earlier stage and improvement of cancer patients' survival and quality of the life. Magnetic resonance imaging (MRI) is a powerful imaging modality for cancer detection and diagnosis. However, current clinically used contrast enhanced MRI is not effective for molecular imaging because of the low sensitivity of MRI and non-specificity of the contrast agents. Safe and effective targeted MRI contrast agents are needed for cancer molecular imaging, in order to accurately detect and diagnose cancers earlier. Recently, we have identified a cancer-related biomarker, oncofetal fibronectin, as a molecular marker for cancer molecular imaging with MRI. Oncofetal fibronectin is abundantly expressed in the stroma of a broad spectrum of human malignant tumors, and rarely in normal tissues [1, 2]. Oncofetal fibronectin promotes tumor angiogenesis and proliferation. Due to its abundance in the tumor stroma, sufficient peptide targeted contrast agents can bind to the cancer-related biomarker to generate significant contrast enhancement to overcome the limitations of MRI in cancer molecular imaging. Since the peptide targeted contrast agents are smaller than the renal filtration threshold, unbound contrast agents can be readily excreted via renal filtration. In this study, we developed a low molecular weight peptide-targeted Gd(III) chelate specific to oncofetal fibronectin for cancer MR molecular imaging. The effectiveness of the agent for cancer MR molecular imaging was evaluated in an orthotopic mouse tumor model.