Synthesis, characterization and in vivo skeletal localization of a new 99mTc based bifunctional multidentate phosphonate chelate: 5-amino-1,3-bis(ethylamine-(N,N dimethyl diphosphonic acid) acetamido) benzene

A new bifunctional multidentate phosphonate ligand was designed, synthesized and characterized by IR, Mass and NMR spectroscopy. The complex was prepared with above 97 % radiochemical purity producing stable 99mTc-chelates with 1:1 complexation with greater numbers of phosphonate groups per molecule than diphosphonates and therefore better-defined preparations. Blood clearance showed a quick wash out from the circulation and biological half life was found to be t1/2 (F)=29 min; t1/2 (S)=3 h 48 min. Excellent quality bone images of rabbit were recorded showing rapid clearance of background activity, visualization of skeleton at 1h and clearance from kidneys. No significant activity in any other soft tissues was noted. Biodistribution carried out in Balb/c mice revealed 5.39 ± 0.96 %ID/g and 7.03 ± 0.14 %ID/g radiotracer uptake in bone at 1h and 4 h respectively which resulted in very high bone-to-muscle ratio. Accumulation in kidneys was found to be 2.67 ± 0.05 % ID/g and 1.96 ± 0.23 % ID/g at 1h and 4 h post injection respectively. The synthesized multidentate phosphonate ligand exhibited good metal ion control properties with very high in vitro stability and possess other useful properties such as high water solubility and chemical stability. This functionalized α-aminomethylene phosphonic acid derivative is suitable for bone imaging as high and selective in vivo bone uptake was seen and can be conjugated to wide variety of vector molecules for therapeutic application