Pyrazolyl conjugates of bombesin: a new tridentate ligand framework for the stabilization of fac-[M(CO)3]+ moiety

We have described the synthesis of tridentate pyrazolyl ligand frameworks for coordination to the fac-[*M(CO)3]+ metal fragment (*M=186/188Re or 99mTc). These ligands impart a degree of kinetic inertness on the metal center, warranting their study in biological systems. We herein report in vitro/in vivo radiolabeling investigations of a new series of pyrazolyl bombesin (BBN) conjugates radiolabeled via the Isolink kit. These new conjugates are based on the general structure [99mTc-pyrazolyl-X-BBN[7–14]NH2], where X=β-alanine, serylserylserine or glycylglycylglycine. The pyrazolyl ligand is a tridentate ligand framework that coordinates the metal center through nitrogen donor atoms. The results of these investigations demonstrate the ability of these new conjugates to specifically target the gastrin-releasing peptide receptor subtype 2, which is overexpressed on human prostate PC-3 cancerous tissues. Therefore, these studies suggest the tridentate pyrazolyl ligand framework to be an ideal candidate for the design and development of low-valent 99mTc-based diagnostic radiopharmaceuticals based on BBN or other targeting vectors.