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Synthesis and biodistribution of a novel 99mTc complex of HYNIC-conjugated metronidazole as a potential tumor hypoxia imaging agent

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Abstract

A conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with the amino analogue of metronidazole (MN) was synthesized through a multiple-step reaction. HYNIC-MN could be labeled easily and efficiently with 99mTc using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) and ethylenediamine -N,N′-diacetic acid (EDDA) as coligands to form the 99mTc–HYNIC–MN complex in high yield (>95%). Its partition coefficient indicated that it was a good hydrophilic complex. The tumor cell experiment showed that the 99mTc–HYNIC–MN complex had a certain hypoxic selectivity. The biodistribution studies of 99mTc–HYNIC–MN in Kunming mice bearing S180 tumor showed a favorable tissue distribution profile with high tumor uptake, and low or negligible accumulation in non-target organs, suggesting 99mTc–HYNIC–MN would be a novel potential tumor hypoxia imaging agent.

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References

  1. Chapman JD (1991) Radiother Oncol 20:13–19

    Article  Google Scholar 

  2. Gatenby RA, Kessler HB, Roeenblum JS, Coia LR, Moldofsky PJ, Harz WH (1988) Int J Radiat Oncol Biol Phys 14:831–838

    Article  CAS  Google Scholar 

  3. Hay MP, Wilson WR, Moselen JW, Palmer BD, Denny WA (1994) J Med Chem 37:381–391

    Article  CAS  Google Scholar 

  4. Cook GJR, Fogelman I (1998) Eur J Nucl Med 25:335–357

    CAS  Google Scholar 

  5. Nunn A, Linder K, Strauss HW (1995) Eur J Nucl Med 22:265–280

    Article  CAS  Google Scholar 

  6. Chu TW, Li RJ, Hu SW, Liu XQ, Wang XY (2004) Nucl Med Biol 31:199–203

    Article  CAS  Google Scholar 

  7. Kong DJ, Lu J, Ye SZ, Wang XB (2007) J Labelled Comp Radiopharm 50:1137–1142

    Article  CAS  Google Scholar 

  8. Mallia MB, Mathur A, Subramanian S, Banerjee S, Sarma HD, Venkatesh M (2005) Bioorg Med Chem Lett 15:3398–3401

    Article  CAS  Google Scholar 

  9. Mallia MB, Subramanian S, Banerjee S, Sarma HD, Venkatesh M (2006) Bioorg Med Chem 14:7666–7670

    Article  CAS  Google Scholar 

  10. Mallia MB, Subramanian S, Mathur A, Sarma HD, Venkatesh M, Banerjee S (2008) Bioorg Med Chem Lett 18:5233–5237

    Article  CAS  Google Scholar 

  11. Zhang Y, Chu TW, Gao XG, Liu XQ, Yang Z, Guo ZQ, Wang XY (2006) Bioorg Med Chem Lett 16:1831–1833

    Article  CAS  Google Scholar 

  12. Zhang JB, Yu Q, Huo JF, Pang Y, Yang S, He YI, Tang TT, Yang CC, Wang XB (2010) J Radioanal Nucl Chem 283:481–485

    Article  CAS  Google Scholar 

  13. Liu S, Edwards DS, Barrett JA (1997) Bioconjug Chem 8:621–636

    Article  CAS  Google Scholar 

  14. Abrams MJ, Juweid M, TenKate CI, Schwartz DA, Hauser MM, Gaul FE, Fuccello AJ, Rubin RH, Strauss HW, Fischman AJ (1990) J Nucl Med 31:2022–2028

    CAS  Google Scholar 

  15. Ohtsuki K, Akashi K, Aoka Y, Blankenberg FG, Kopiwoda S, Tait JF, Strauss HW (1999) Eur J Nucl Med 26:1251–1258

    Article  CAS  Google Scholar 

  16. Steffens MG, Oosterwijk E, Kranenborg MHGC, Manders JMB, Debruyne FMJ, Corstens FHM, Boerman OC (1999) J Nucl Med 40:829–836

    CAS  Google Scholar 

  17. Ono M, Arano Y, Mukai T, Fujioka Y, Ogawa K, Uehara T, Saga T, Konishi J, Saji H (2001) Nucl Med Biol 28:215–224

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The work was financially supported by the Fundamental Research Funds for the Central Universities of China (FRF-BR-09-006A) and by the International Science and Technology Cooperation Program of China (ISTCP) (2008AR), the Ministry of Science and Technology of the People’s Republic of China. The radiochemical data were acquired at Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education. The authors thank Dr. Zhang Shijian for his help with the animal experiments.

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Authors and Affiliations

  1. Department of Biological Science and Engineering, School of Chemical and Biological Engineering, University of Science and Technology Beijing, 30th Xueyuan Road, Haidian District, Beijing, 100083, People’s Republic of China

    Liqin Liu, Min Zhang & Guangrong Zhong

  2. Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, People’s Republic of China

    Xuebin Wang

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  1. Liqin Liu
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  2. Min Zhang
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  3. Guangrong Zhong
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  4. Xuebin Wang
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Correspondence to Liqin Liu.

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Liu, L., Zhang, M., Zhong, G. et al. Synthesis and biodistribution of a novel 99mTc complex of HYNIC-conjugated metronidazole as a potential tumor hypoxia imaging agent. J Radioanal Nucl Chem 287, 847–852 (2011). https://doi.org/10.1007/s10967-010-0889-6

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  • DOI: https://doi.org/10.1007/s10967-010-0889-6

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