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

摘要

A new bifunctional multidentate phosphonate ligand was designed, synthesized and characterized by IR, Massand NMR spectroscopy. The complex was prepared with above 97 % radiochemical purity producing stable 99mTc-chelateswith 1:1 complexation with greater numbers of phosphonate groups per molecule than diphosphonates and therefore betterdefinedpreparations. Blood clearance showed a quick wash out from the circulation and biological half life was found tobe t? (F)=29 min; t? (S)=3 h 48 min. Excellent quality bone images of rabbit were recorded showing rapid clearance ofbackground activity, visualization of skeleton at 1h and clearance from kidneys. No significant activity in any other softtissues was noted. Biodistribution carried out in BALB/c mice revealed 5.39 ± 0.96 %ID/g and 7.03 ± 0.14 %ID/gradiotracer uptake in bone at 1h and 4 h respectively which resulted in very high bone-to-muscle ratio. Accumulation inkidneys 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. Thesynthesized multidentate phosphonate ligand exhibited good metal ion control properties with very high in vitro stabilityand possess other useful properties such as high water solubility and chemical stability. This functionalised α-aminomethylene phosphonic acid derivative is suitable for bone imaging as high and selective in vivo bone uptake wasseen and can be conjugated to wide variety of vector molecules for therapeutic application. Abbreviations: Am-IPTMP,amino-isophthalic tetramethylenephosphonate, BFC Bifuctional chelating agent