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 synth esis 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 ch aracterized with respect to their photophysical properties and tested ill v itro for their ability to bind to tumor cells and in vivo for their potenti al to delineate experimental tumors. In contrast to HAS-ITTC, Tf-ITCC showe d receptor-mediated uptake by HT29 human colon cancer cells in vitro. After intravenous injection into HT29 tumor-bearing nude mice both compounds ind uced increased fluorescence contrast of tumors in vivo. After 24 h the cont rast between tumor and normal tissue was significantly higher for Tf-ITCC t han for HAS-ITCC. Dye-induced fluorescence was found to be predominantly lo cated in perinecrotic areas of the tumor. Furthermore, Tf-ITCC produced flu orescence of viable tumor cells, whereas HAS-ITCC fluorescence was recorded along connective tissue, We conclude that ITCC-labeled Tf and HSA can serv e as macromolecular contrast agents for the optical imaging of tumors, with Tf-ITCC showing higher efficiency.