An Effective Targeted Nanoglobular Manganese(II) Chelate Conjugate for Magnetic Resonance Molecular Imaging of Tumor Extracellular Matrix

Abstract

Stable manganese(II) chelates are of great interest for the design and development of safe and effective non-gadolinium(III)-based targeted MRI contrast agents for MR cancer molecular imaging. In this study, a CLT1 peptide targeted G3 nanoglobular Mn(II)-DOTA monoamide conjugate was designed and synthesized as a targeted MRI contrast agent for molecular imaging of the fibrin-fibronectin complexes or oncofetal fibronectin in tumor stroma. The targeted contrast agent comprised 2 peptides and 42 Mn(II)-DOTA chelates on the surface of the G3 nanoglobule. The T(1) and T(2) relaxivities of the targeted agent at room temperature were 3.13 and 8.74 mM(-1) s(-1) per Mn(II) chelate at 3 T (tesla), respectively. It had a well-defined nanosize (5.2 nm) and could be readily excreted via renal filtration. The targeted nanoglobular contrast agent specifically bound to tumor tissue, resulting in significant tumor contrast enhancement with minimal nonspecific enhancement in the liver of tumor bearing mice as compared to a nontargeted control at a dose as low as 0.03 mmol-Mn/kg. The targeted G3 nanoglobular Mn(II)-DOTA conjugate is promising as a targeted non-gadolinium(III)-based MRI contrast agent for MR cancer molecular imaging.