Site-specific tumor targeted fluorescent contrast agents

Site-specific delivery of drugs and contrast agents to tumors protects normal tissues from the cytotoxic effect of drugs, and enhances the contrast between normal and diseased tissues. In optical medicine, biocompatible dyes can be used as phototherapeutics or as contrast agents. Previous studies have shown that the use of covalent or non-covalent dye conjugates of carriers such as antibodies, liposomes, and polysaccharides improves the delivery of such molecules to tumors. However, large biomolecules can elicit adverse immunogenic reactions and also result in prolonged blood circulation times, delaying visualization of target tissues. A viable alternative to this strategy is to use small bioactive molecule-dye conjugates. These molecules have several advantages over large biomolecules, including ease of synthesis of a variety of high purity compounds for combinatorial screening of new targets, enhanced diffusivity to solid tumors, and the ability to affect the pharmacokinetics of the conjugates by minor structural changes. Thus, we conjugated a near infrared light absorbing dye to bioactive peptides that specifically target overexpressed tumor receptors in established rat tumor lines. High tumor uptake of the conjugates was obtained without loss of either-the peptide receptor affinity or the dye fluorescence. These findings demonstrate the efficacy of a small peptide-dye conjugate strategy for in vivo tumor imaging. Site-specific delivery of photodynamic therapy agents may also benefit from this approach.