Synthesis, characterization and biological studies of rhenium, technetium-99m and rhenium-188 pentapeptides

A pentapeptide macrocyclic ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for SPECT imaging and therapeutic in vivo agents. This study shows the synthesis and characterization of KYCAR complexes containing nonradioactive rhenium, ^99mTc, or ¹⁸⁸Re. The metal complexes were also biologically evaluated to determine in vivo distribution in healthy mice. The overall goals of this project were (1) to synthesize the Tc/Re pentapeptide complexes, (2) to identify spectroscopic methods for characterization of syn versus anti rhenium peptide complexes, (3) to analyze the ex vivo stability, and (4) to assess the biological properties of the [^99mTc]TcO-KYCAR and [¹⁸⁸Re]ReO-KYCAR complexes in vivo. Details on these efforts are provided below.