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Macromolecular Contrast Agents for Optical Imaging of Tumors: Comparison of Indotricarbocyanine‐labeled Human Serum Albumin and Transferrin ¶

Macromolecules accumulate in solid tumors and can thus be used as carriers for the delivery of attached contrast agents to tumors. We report the synthesis and use of serum protein–dye conjugates consisting of transferrin (Tf) or human serum albumin (HSA) and an indotricarbocyanine (ITCC) derivative as contrast agents for the optical imaging of tumors. The compounds were characterized with respect to their photophysical properties and tested in vitro for their ability to bind to tumor cells and in vivo for their potential to delineate experimental tumors. In contrast to HAS‐ITTC, Tf‐ITCC showed receptor‐mediated uptake by HT29 human colon cancer cells in vitro. After intravenous injection into HT29 tumor‐bearing nude mice both compounds induced increased fluorescence contrast of tumors in vivo. After 24 h the contrast between tumor and normal tissue was significantly higher for Tf‐ITCC than for HAS‐ITCC. Dye‐induced fluorescence was found to be predominantly located in perinecrotic areas of the tumor. Furthermore, Tf‐ITCC produced fluorescence of viable tumor cells, whereas HAS‐ITCC fluorescence was recorded along connective tissue. We conclude that ITCC‐labeled Tf and HSA can serve as macromolecular contrast agents for the optical imaging of tumors, with Tf‐ITCC showing higher efficiency.