Research of Novel Bifunctional Chelating Agents for the Tc-tricarbonyls Precursor［~(99)Tc~m(CO)_3(H_2O)_3］~+

The organometallic precursor fac-［~(99)Tc~m(OH_2)_3(CO)_3］~+ is reacted with three novel tridentate ligands (NNS-1,NNS-2,NSN) and the propertices of their ~(99)Tc~(m) compleses in vivo and in vitro have been evaluated.One tridentate ligand (NNO),which has been reported by Alberto R.ect.,is also synthesized. The results of labeling condition experiments indicate that a radiochemical purity higher than 90% can be obtained within a very short time (10 min) by the reaction of fac-［~(99)Tc~m(CO)_3］~+ core in a slightly acidic condition (pH=4.0～6.0) with a very small amount (10 μg) of these three new ligands. Two of the complexes (NNS-1,NNS-2) are electrically neutral and lipophilic evidenced by electrophoretic investigations.And another comples (NSN) is cationic and hydrophilic.It showe that the three ligands can be used as alternative bifumctional chelating ligands at different conditions. Stablility experiments and competition experiments with glutathion (GSH) and L -cysteine respectively show that the three novel tridentate complexes have a high stability in vitro . Biodistribution studies in mice demonstrate all three complexes are fast cleared from the blood and organs other than liver.Two of the complexes (NNS-1,NNS-2)have some uptake in heart,and fast clearance and have low uptake in brain.