Study On ～(99)Tc～m-HMIBP As A New Bone-imaging Agent

Bisphosphonates with a imidazole ring have higher affinity for bone mineral,and zoledronate is just a good example which is extensively used clinically for the treatment of patients with tumour-induced hypercalcaemia and osteolytic bone metastases. 1-Hydroxy-2-(1-methylimidazol-2-yl)ethylidene-1,1-bisphosphonic acid(HMIBP)that has the similar structure to zoledronic acid,is therefore considered potentially useful as a bone-imaging agent if labeled with 99Tcm,which has not been reported in and abroad. 99Tcm-HMIBP was therefore prepared for bone imaging in order to develop a new excellent bone-imaging agent.HMIBP was synthesized by four steps from the raw material 1-methl imidazole. 99Tcm-HMIBP was prepared by the reduction of 99Tcm-pertechnetate in the presence of SnCl2˙2H2O.The effects of the amounts of SnCl2˙2H2O and HMIBP,and pH value on the radiochemical purity and labeling yield of 99Tcm-HMIBP were investigated.Meantime, 99Tcm-HMIBP kit was prepared and some properties such as shape character, HMIBP purity,pH value,labeling method and yield,stability were controlled.Some biological characters including pharmacokinetics,plasma protein binding ratio,partition coefficients,acute toxicity,biodistribution and bone scan were studied;also a comparison among 99Tcm-HMIBP, 99Tcm-MIDP and 99Tcm-MDP was made.HMIBP and intermediates were all identified by IR,elementary analysis,MS and HNMR. When the amounts of HMIBP and SnCl2˙2H2O were more than 2.5mg and 10μg,respectively;the pH value was between 2 and 6 ,and the labeling reaction continued for 10min,both radiochemical purity and labeling yield of 99Tcm-HMIBP were over 90% and remained within 6 hours.The pharmacokinetic equation was C=3.097947exp(-0.072086t)+0.125000exp(-0.007636t) ,the plasma protein binding rate and partition coefficients were 44.77% and 0.0125(pH7.0),0.0054(pH7.4), LD50 was 8.2mg/kg.The results of biodistribution and bone scan showed that the bone uptake was up to 7.94%ID/g at 30min after injection of 99Tcm-HMIBP,bone-to-muscle and bone-to-blood uptake ratios were 20.89 and 16.89,respectively.The clear bone image was obtained at 120min after injection of 99Tcm-HMIBP and clearance in renal was visible.The bone-imaging of 99Tcm-HMIBP is superior to 99Tcm-MIDP and is correspond to 99Tcm-MDP .The preparation of 99Tcm-HMIBP is convenient and 99Tcm-HMIBP has good stability,which express that 99Tcm-HMIBP is an excellent bone-imaging agent and is worth developing.