Preparation And Biological Evaluation Of ⁹⁹Tc^m-PIDP And ⁹⁹Tc^m-EMIDP As Bone Imaging Agents

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-( 2-propyl-1H-imidazol-1-yl ) ethane-1,1-diyldiphosphonic acid (PIDP), 1-hydroxy-2-(2-ethyl-4-methyl-1H-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid(EMIDP) that have the similar structure to zoledronic acid, are new compounds and considered potentially useful as bone-imaging agents if labeled with 99Tcm, which have not been reported in and abroad. 99Tcm-PIDP and 99Tcm-EMIDP were prepared and studied. The SPECT imiaging was carried out to evaluate their feasibilities as novel bone imaging agents.PIDP and EMIDP were synthesized by three steps from the raw material 2-proyl-1H-imidazol and 2-ethyl-4-methyl-1H-imidazol, respectively. 99Tcm-PIDP and 99Tcm-EMIDP were prepared by the reduction of 99Tcm-pertechnetate in the presence of SnCl2˙2H2O. The effects of the amounts of 99TcmO4-, SnCl2˙2H2O, PIDP, EMIDP and pH value on the radiochemical purity and labeling yield of 99Tcm-PIDP and 99Tcm-EMIDP were investigated. Meantime, Some biological characters including plasma protein binding ratio, partition coefficients, biodistribution and bone scan were studied, and a comparison among 99Tcm-ZL and 99Tcm-MDP was made.PIDP, EMIDP and intermediates were all identified by elementary analysis, IR, MS and 1H-NMR. 99Tcm-PIDP and 99Tcm-EMIDP were radiolabeled successfully with 99Tcm. The plasma protein binding rates of 99Tcm-PIDP and 99Tcm-EMIDP were 22.78% and 23.16%, respectively. And partition coefficients were 0.012 and 0.0048 (pH7.0), were 0.016 and 0.0061 (pH7.4), respectively. The results of biodistribution showed that the bone uptake were up to 8.47%ID/g and 7.82%ID/g at 30 min after injection of 99Tcm-PIDP and 99Tcm-EMIDP, respectively. Bone-to-muscle uptake ratios were 21.23 and 22.56, and bone-to-blood uptake ratios were 5.80 and 5.39, respectively. The clear bone images were obtained at 2 hours after injection of 99Tcm-PIDP and 99Tcm-EMIDP. The bone-imaging of 99Tcm-PIDP and 99Tcm-EMIDP are superior to 99Tcm-ZL and are correspond to 99Tcm-MDP. So, 99Tcm-PIDP and 99Tcm-EMIDP are worthy of further investigation and they would be used as novel excellent bone imaging agents for skeletal imaging in future.