Two New Bone Imaging Agent - <sup> 99m </ Sup> Tc-heidp <sup> 99m </ Sup> Tc-hbidp Preparation And Research

Bisphosphates are known to have high affinity for bone mineral. Especially for the third-generation of bisphosphonate-zoledronate, the introduction of the nitrogen to the side chain of imidazole ring have showed high efficacy.Two novel zoledronic acid derivatives,2-(1-ethyl-1H-imidazol-2-yl)-1-hydroxy--ethane-l,1-diyldiphosphonic acid (HEIDP) and 2-(1-butyl-1H-imidazol-2-yl)-1--hydroxyethane-l,l-diyldiphosphonic acid (HBIDP) were prepared by hydroxymethy--lation, bromination, cyano substitution, acid hydrolysis and phosphine acylation from the raw material 1-ethyl-1H-imidazole and 1-butyl-1H-imidazole respectively. The intermediate products and the target product were confirmed by elemental analysis, IR, MS and 1HNMR techniques.The two novel zoledronic acid derivatives were further labeled with Tc to prepared 99mTc-HEIDP and 99mTc-HBIDP. The reaction conditions such as the amount of ligand and SnCl2·2H2O, the activity of 99mTcO4-, pH value and the reaction time were investigated, the optimum conditions of labeling reaction were established. Paper chromatography (TLC) and HPLC were applied into evaluation the quality of this two 99mTc-labeled Zoledronic acid derivatives. The optimum conditions was determined as following:the amount of ligand and SnCl2·2H2O were 5 mg and 100μg, respectively, the activity of 99mTcO4- was 55.5 MBq, pH value was between 4 and 6, and the reaction time was 20 min at room temperature, Which can make the radiochemical efficiency of this two radioactive drugs are greater than 95%.The pharmacokinetics and biodistribution studies in mice, SPECT bone scan in rabbits as well as plasma protein binding ratios and partition coefficients were also investigated to evaluate their biological properties. A comparison among 99mTc-HEIDP, 99mTc-HBIDP and 99mTc-MDP were also made. The pharmacokinetics and biodistribution experimental results showed that this two labeled complex both have significant selective bone uptake, rapid clearance from blood and other organs, which made them desirable for further investigation as novel bone imaging agents. Compared with 99mTc-MDP, the bone uptakes of 99mTc-HEIDP and 99mTc-HBIDP have reached to 7.62%ID/g and 9.07%ID/g at 30 min respectively, whereas those of 99mTc-MDP were 4.79%ID/g. And the uptake ratios of bone to soft tissues of 99mTc-HEIDP and 99mTc-HBIDP were also notably higher than those of 99mTc-MDP. What's more, these two labeled complex need less imaging time and have superior imaging effect. On the whole, these two designed novel 99mTc-labeled-Zoledronic acid derivatives are worthy of further investigation and could be used as bone imaging agent in future.