ABSTRACT
Easily synthesised and structurally well-defined novel imaging/therapeutic radiopharmaceutical agents for bone metastases are described.
Subject(s)
Bone Neoplasms , Diphosphonates/therapeutic use , Organotechnetium Compounds/chemistry , Radiopharmaceuticals , Rhenium/chemistry , Animals , Bone Neoplasms/diagnosis , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/drug therapy , Female , Humans , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred BALB C , Molecular Structure , Organotechnetium Compounds/therapeutic use , Radionuclide Imaging , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/therapeutic useABSTRACT
The activity of a Zn(II) complex of a tetradentate, tripodal ligand for catalyzing phosphodiester cleavage is enhanced 750-fold by introducing three hydrogen bond donors to the ligand. Inhibition studies show that the Zn-aqua complex is the kinetically active form and that it binds the transition state with a formal dissociation constant of 3 x 108 M-1. The effect of these ligand modifications on the transition-state affinity is comparable to the rate acceleration provided by the metal ion itself. Overall, this mononuclear complex is more active than the most reactive dinuclear Zn(II) complexes reported to date.
