Cyanine dyes as contrast agents in biomedical optical imaging.

As light exhibits highest penetration into living tissue in the near-infrared (NIR) region between 700 and 900 nm, tissue probing with NIR light provides the opportunity to detect tumors or other abnormalities up to several centimeters below the tissue surface (1). To gain a deeper understanding of physiological and molecular processes in vivo, an important role is increasingly attributed to the acquisition of optical signals generated by exogenously administered fluorescent probes (2–4). Particularly, NIRabsorbing cyanine dyes are potentially suited as fluorescent contrast agents, e.g. for fluorescence-guided endoscopy or optical mammography (1). The fact, that fluorescent dyes can be detected at low concentrations and nonionizing, harmless radiation can be applied repeatedly to the patient renders this technology particularly attractive. In the area of organic dyes, the class of cyanine dyes has proven to be most promising for biomedical applications (5). Thus, the objective of our work is the synthesis of novel cyanine dyes and their characterization as fluorescent contrast agents. Following different concepts, a hydrophilic indotricarbocyanine, which is supposed to act as extracellular contrast agent similar to MR agents, was studied on the one hand. In a different approach we demonstrate that receptor-mediated intracellular tumor targeting using cyanine dye-labeled peptides, which are structurally derived from natural ligands of heptahelical receptors, is a feasible way to achieve specific accumulation and high contrasts in animal tumors. One particular approach was adapted from the radiodiagnostic agent OctreoScan® and involved the use of the peptide octreotate which is known to effectively bind to the somatostatin receptor (SSTR).