title: Pyrazolyl conjugates of bombesin: a new tridentate ligand framework for the stabilization of fac-[M(CO)3]+ moiety.
abstract: We have described the synthesis of tridentate pyrazolyl ligand frameworks for coordination to the fac-[*M(CO)(3)](+) metal fragment (*M=(186/188)Re or (99m)Tc). 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 [(99m)Tc-pyrazolyl-X-BBN[7-14]NH(2)], where X=beta-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 (99m)Tc-based diagnostic radiopharmaceuticals based on BBN or other targeting vectors.
authors.affiliation: Departamento de Química, Instituto Tecnológico e Nuclear, 2686-953 Sacavém, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Alves
authors.forename: Joao D G
authors.initials: JD
authors.lastname: Correia
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
authors.forename: Bhadrasetty
authors.initials: B
authors.lastname: Veerendra
authors.forename: Gary L
authors.initials: GL
authors.lastname: Sieckman
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hoffman
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Rold
authors.forename: Said Daibes
authors.initials: SD
authors.lastname: Figueroa
authors.forename: Lauren
authors.initials: L
authors.lastname: Retzloff
authors.forename: Joseph
authors.initials: J
authors.lastname: McCrate
authors.forename: Adam
authors.initials: A
authors.lastname: Prasanphanich
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Smith
mesh_terms: D000818:Animals; D001839:Bombesin / Q000493:pharmacokinetics*; D004355:Drug Stability; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D016513:Mice, SCID; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D047069:Pyrazolones / Q000493:pharmacokinetics; D011869:Radioligand Assay / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D008024:Ligands; D047069:Pyrazolones; D019275:Radiopharmaceuticals; D001839:Bombesin