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

• Published in: Nuclear medicine and biology Vol. 33; no. 5; pp. 625 - 634
• Main Authors: Alves, Susana, Correia, Joao D.G., Santos, Isabel, Veerendra, Bhadrasetty, Sieckman, Gary L., Hoffman, Timothy J., Rold, Tammy L., Figueroa, Said Daibes, Retzloff, Lauren, McCrate, Joseph, Prasanphanich, Adam, Smith, Charles J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2006
• Subjects: Animals; Bombesin; Bombesin - pharmacokinetics; Carbonyl; Conjugates; Drug Stability; Humans; Isotope Labeling - methods; Ligands; Male; Metabolic Clearance Rate; Mice; Mice, SCID; Organ Specificity; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - metabolism; Pyrazolones - pharmacokinetics; Radioligand Assay - methods; Radionuclide Imaging; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Technetium; Tissue Distribution; Conjugates; Technetium; Bombesin; Carbonyl
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2006.03.007

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]NH
2], 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.