Biomacromolecules, Vol.11, No.3, 754-761, 2010
Peptide-Targeted Nanoglobular Gd-DOTA Monoamide Conjugates for Magnetic Resonance Cancer Molecular Imaging
Effective imaging of a cancer molecular biomarker is critical for accurate cancer diagnosis and prognosis. CLT1 peptide was observed to specifically bind to the fibrin-fibronectin complexes presented ill tumor extracellular matrix. In this study, we synthesized and evaluated CLT1 peptide-targeted nanoglobular Gd-DOTA monoamide Conjugates for magnetic resonance (MR) imaging of the fibrin-fibronectin complexes in tumor. The targeted nanoglobular contrast agents were prepared by Conjugating peptide CLT1 to G2 and G3 nanoglobule (lysine dendrimers with a Cubic silsesquioxane core) Gd-DOTA monoamide conjugates via click chemistry. The T, relaxivities of peptide-targeted G2 and G3 nanoglobules were 7.92 and 8.20 mM(-1) s(-1) at 3T, respectively. Approximately 2 peptides and 25 Gd-DOTA chelates were conjugated onto the Surface of 32 airline groups of G2 nanoglobule, and 3 peptides and 43 Gd-DOTA chelates onto file Surface of 64 airline groups of G3 nanoglobule. The peptide-targeted nanoglobular contrast agents showed greater contrast enhancement than the corresponding nontargeted agents in tumor at a dose of 0.03 mmol-Gd/kg in female athymic mice hearing MDA-MB-231 human breast carcinoma xenografts. The targeted MRI contrast agents have a potential for specific cancer molecular imaging with MRI.