| Bisphosphonates with a imidazole ring, such as zoledronic acid(ZL), have higher affinity for bone mineral.They are extensively used clinically for the treatment of patients with tumour-induced hypercalcaemia andosteolytic bone metastases. 2-(1H-1,2,4-triazol-1-yl)- 1-hydroxyethane-1,1-diphosphonic acid(TADP) which we studied also has a ring of five molecule, the difference between TADP and ZL is that TADP has three nitrogen molecule. 99Tcm- TADP has not been reported in and abroad. It is therefore considered potentially useful as a bone-imaging agent. 99Tcm-TADP was therefore prepared for bone imaging in order to develop a new excellent bone-imaging agent.TADP was synthesized by three steps from the raw material 1H-1,2,4-triazole. 99Tcm- TADP was prepared by the reduction of 99Tcm-pertechnetate in the presence of SnCl2˙2H2O.The effects of the amounts of SnCl2˙2H2O and TADP, and pH value on the radiochemical purity and labeling yield of 99Tcm-TADP were investigated. Some biological characters including pharmacokinetics, plasma protein binding ratio, partition coefficients, biodistribution and bone scan were studied, and a comparison among 99Tcm-TADP, 99Tcm-ZL and 99Tcm-MDP was made.TADP and intermediates were all identified by IR,elementary analysis,MS and 1HNMR. When the amounts of TADP and SnCl2˙2H2O were more than 3.0mg and 50μg,respectively;the pH value was between 3 to 7 ,and the labeling reaction continued for 15min,both radiochemical purity and labeling yield of 99Tcm-TADP were over 90%.The pharmacokinetic equation was C=885.614exp(-3.983t)+36.817exp(-0.142t),the plasma protein binding rate and partition coefficients were 18.54% and 0.0012 (pH7.0),0.0031(pH7.4) respectively.The results of biodistribution showed that the bone uptake was up to 17.17%ID/g at 30min after injection of 99Tcm-TADP,bone-to-muscle and bone-to-blood uptake ratios were 61.32 and 13.21,respectively.The clear bone image was obtained at 120min after injection of 99Tcm-TADP and clearance in renal was visible.The bone-imaging of 99Tcm-TADP is superior to that of 99Tcm-ZL and is correspond to that of 99Tcm-MDP.99Tcm-TADP is a new imaging agent after ZL, has good stability, and is worth developing. Key words: TADP, 99Tcm-TADP, pharmacokinetics, biodistribution, bone-imaging... |
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