Synergistic Effect of Human Serum Albumin and Fullerene on Gd-DO3A for Tumor-Targeting Imaging.

ABSTRACT

A macromolecular magnetic resonance imaging (MRI) contrast agent was successfully synthesized by conjugating the gadolinium/1,4,7,10-tetraazacyclododecane-1,4,7-tetracetic acid complex (Gd-DO3A) with 6,6-phenyl-C61 butyric acid (PC61BA) and upon further modification with human serum albumin (HSA). The final product, PC61BA-(Gd-DO3A)/HSA, has a high stability and exhibits a much higher relaxivity (r1 = 89.1 mM(-1) s(-1) at 0.5 T, 300 K) than Gd-DO3A (r1 = 4.7 mM(-1) s(-1)) does under the same condition, producing the synergistic positive effect of HSA and C60 on the relaxivity of Gd-DO3A. The in vivo MR images of PC61BA-(Gd-DO3A)/HSA-treated tumor-bearing mice show strong signal enhancement for the tumor area due to the enhanced permeability and retention effect. The maximum accumulation of PC61BA-(Gd-DO3A)/HSA at the tumor site was achieved at 4 h postinjection, which may guide surgery. The results from the hematology and histological observations indicate that PC61BA-(Gd-DO3A)/HSA has no obvious toxicity in vivo. These unique properties of PC61BA-(Gd-DO3A)/HSA enable them to be highly efficient for tumor-targeting MRI in vivo, possibly providing a good solution for tumor diagnosis.