Preparation and Reaction Kinetics of a New Bone Imaging Agent ⁹⁹Tc^m-BIPrDP

A new diphosphonic acid ligand, 1-hydroxy 3-(2-butyl-1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid (BIPrDP), was prepared from the starting material 2-butyl-1H-imidazole by three steps of reactions: N-alkylation, ester hydrolysis and phosphoric acid acylation. The structures of the intermediate and target compounds were identified by elemental analysis, MS and ¹H-NMR. BIPrDP was directly labeled by Na⁹⁹Tc^mO₄ in the presence of the reducing agent SnCl₂ to afford a new bone imaging agent ⁹⁹Tc^m-BIPrDP. The kinetics of the labeling reaction between BIBrDP and ⁹⁹Tc^mO₄^- was also studied. The reaction rate constants, k, were determined to be 0.018 3, 0.020 7, 0.024 1, 0.027 0, 0.028 8, 0.031 9 at 40、50、60、70、80 and 90 ℃, respectively. The correlation between the reaction rate constant k and temperature T was ln k =-1 267.1×(1/T)+0.055（r²=0.990 2). The reaction activation energy, E_a, was found to be 10.53 kJ·mol^-1, much lower than the activation energy of general chemical reactions (typically 20~150 kJ·mol^-1), which was consistent with the observation that the preparation of ⁹⁹Tc^m-BIPrDP took place rapidly. In addition, based on the data of the radiolabeling yield (RLY) at different temperatures, a correlation between the RLY and temperature was developed as lnRLY/(1－RLY)=-6 218.4/T+19.84. This correlation suggests that, in order to achieve radiolabeling yields of higher than 90%, the reaction temperature should be higher than 79.31 ℃.