Preparation and evaluation of 99mTc-labeled cyclic arginine-glycine-aspartate (RGD) peptide for integrin targeting.

Technetium coordination chemistry has been a subject of interest in the development of radiopharmaceuticals, especially imaging radiotracers. Due to the extensive work done on developing chelates for (99m)Tc, various chelators have been investigated and applied to radiopharmceuticals. Previous studies on the coordination chemistry of the [(99m)Tc=O] core have established peptide-derived sequences as effective chelating ligands. These observations led to the design of tetradentate ligands derived from amino acid sequences. Such amino acid sequences provide a tetradentate coordination site for chelation to the radionuclide and an effective functional group for conjugation to biomolecules using conventional solid-phase synthetic routes. A derivative of a novel tripeptide chelating sequence, Pro-Gly-Cys (PGC) has been developed where it is possible to form stable technetium complexes with the [(99m)Tc=O] via N(3)S(1) tetradentate coordination core that serves this function and can be readily incorporated into biomolecules using solid-phase synthesis techniques. As a model system, the RGD peptide was selected which has been well known to target the integrin receptor for angiogenesis and tumor imaging agents. The results of in vivo studies with these novel radiolabeled compounds in tumor xenografts demonstrated a distribution in tumor targeting and other organs, such as kidney, liver and intestines.