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99mTc-labeled butyl-substituted zoledronic acid as a novel potential SPECT imaging agent: preparation and preclinical pharmacology study

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Abstract

Zoledronic acid (ZL) is the most potent among the tested diphosphonates. To develop a superior bone imaging agent that could improve the efficiency of bone scanning, an optimized radiotracer was designed from ZL and prepared successfully, 99mTc-BIDP [BIDP, 1-hydroxy-2-(2-butyl-1H-imidazole-1-yl) ethylidene-1,1-diphosphonic acid]. It possesses high radiolabeling yield, radiochemical purity, and stability. The biodistribution in mice shows that 99mTc-BIDP has high specificity in the skeleton with the maximum uptake of 24.6 ± 1.65 % ID g−1 at 120 min post injection. It can be quickly absorbed and rapidly eliminated from the blood judged from the short distribution half-life (t 1/2α  = 1.65 min) and elimination half-life (t 1/2β  = 30.91 min). The bone imaging of the rabbit showed that 99mTc-BIDP has highly selective uptake in the skeletal system and rapid clearance from the soft tissues. An excellent scintigraphic image can be obtained at 1 h with clear visualization of the skeleton.

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (20801024 and 21001055), Key Medical Talent Project of Jiangsu Province (RC2011097) and Public Service Platform for Science and Technology Infrastructure Construction Project of Jiangsu Province (BM2012066). The authors also wish to thank Dr Wanzhong Ye for his assistance in the SPECT scanning.

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Authors and Affiliations

  1. Key Laboratory of Nuclear Medicine of Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China

    Ling Qiu, Jianguo Lin, Wen Cheng, Yan Wang & Shineng Luo

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  1. Ling Qiu
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  2. Jianguo Lin
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  3. Wen Cheng
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  4. Yan Wang
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  5. Shineng Luo
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Correspondence to Jianguo Lin.

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Qiu, L., Lin, J., Cheng, W. et al. 99mTc-labeled butyl-substituted zoledronic acid as a novel potential SPECT imaging agent: preparation and preclinical pharmacology study. Med Chem Res 22, 6154–6162 (2013). https://doi.org/10.1007/s00044-013-0613-5

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  • DOI: https://doi.org/10.1007/s00044-013-0613-5

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