Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform

We have designed, synthesized, and evaluated the efficacy of novel dye-pept ide conjugates that are receptor specific. Contrary to the traditional appr oach of conjugating dyes to large proteins and antibodies, we used small pe ptide-dye conjugates that target overexpressed receptors on tumors. Despite the fact that the peptide and the dye probe have similar molecular mass, o ur results demonstrate that the affinity of the peptide for its receptor an d the dye fluorescence properties are both retained. The use of small pepti des has several advantages over large biomolecules, including ease of synth esis of a variety of compounds for potential combinatorial screening of new targets, reproducibility of high purity compounds, diffusiveness to solid tumors, and the ability to incorporate a variety of functional groups that modify the pharmacokinetics of the peptide-dye conjugates. The efficacy of these new fluorescent optical contrast agents was evaluated in vivo in well -characterized rat tumor lines expressing somatostatin (sst(2)) and bombesi n receptors. A simple continuous wave optical imaging system was employed. The resulting optical images clearly show that successful specific tumor ta rgeting was achieved. Thus, we have demonstrated that small peptide-dye con jugates are effective as contrast agents for optical imaging of tumors. (C) 2001 Society of Photo-Optical Instrumentation Engineers.