Abstract
Many tumor cells are characterized by the overexpression of highly specific transferrin receptors. Transferrin is bound to its receptor, which is followed by rapid internalization into intracellular compartments; it can thus be used for the specific delivery of coupled contrast agents in to tumor cells. The aim of our study was to investigate the tumor- specificity of transferrin-modified contrast agents for optical imaging and magnetic resonance imaging (MRI). Indotricarbocyanine, a near-IR absorbing dye, and ultrasmall superparamagnetic iron oxide particles, a contrast material for MRI, were covalently coupled to transferrin and examined in vitro and in vivo for their potential as tumor-specific contrast agents. CEll culture experiments using HT29 and A431 tumor cells showed specific uptake of transferrin- modified contrast agents by the cells at 37 degrees C, while uptake was inhibited at 4 degrees C or in the presence of an excess of unlabeled transferrin. Optical imaging of tumor- bearing nude mice after intravenous injection of transferrin-ICC resulted in pronounced tumor fluorescence. Tumor specificity was also observe in MRI, where transferrin-USPIO accumulated in SMT2A tumor-bearing rats. We conclude that transferrin-modified contrast agents for optical imaging and MRI can be specifically delivered to tumor tissue by use of transferrin receptor pathways.
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