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Objective: Bone scintigraphy with 99mTc-labeled diphosphonates is one of the most widely used methods for diagnosis and surveillance of bone metastases.The purpose of this study was to extension and optimization of the linker chain between the imidazolyl and geminal diphosphonate group in the typical third-generation diphosphonate of zoledronic acid (ZL) to develop an excellent SPECT imaging agent.Methods: Thirty five normal ICR mice were used to determine the distribution of 99mTc-IBDP (IBDP=1-hydroxy-4-(1 H-imidazol-1-yl) butane-1, 1-diyl diphosphonic acid) in various organs.The mice were divided into seven groups and sacrificed at different time points after the injection of 1.85 MBq 99mTc-IBDP.Samples of heart, liver, spleen, lung, kidney, bone, muscle, stomach,brain and blood were counted by a well-type γ counter to determine the residual activity.And the biodistribution properties of 99mTc-IPrDP were further compared with those of 99mTc-ZL.For pharmacokinetic study, a series of blood samples (0.1 mL) were collected in the microcapillary tube by nicking the tail with a needle at 10, 30, 60, 90, 120, 180, 240 and 360 min after administration of 99mTc-IPrDP and 99mTc-ZL respectively.Results: 99mTc-IBDP shows highly selective uptake in the skeletal system and low uptakes in non-target.The bone uptake increased continuously to a maximum of 13.11%ID/g at 120 min after injection of 99mTc-IBDP, which was larger than that of 99mTc-ZL (11.72 %ID/g).The liver and heart uptakes of 99mTc-IBDP were lower than those of 99mTc-ZL, but the kidney uptake of 99mTc-IBDP was larger than that of 99mTc-ZL, indicating it can be excreted rapidly from the kidney.The pharmacokinetic studies also indicate that 99mTc-IBDP can be more quickly absorbed and rapidly eliminated from the blood than 99mTc-ZL.Conclusions: 99mTc-IBDP exhibited high uptake in bone and relatively low uptake in soft tissues,indicating that it holds potential applications as a novel bone-seeking agent for diagnosis of bone metastases and judging the therapeutic effect of IBDP on bone metastases.