Log in

Evaluation of 99mTc-labeled glutathione as a colon cancer targeting probe

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

The present study was designed to unravel the bioevaluation of [99mTc]Tc-GSH in HT 29 colon cancer cell line as well as in experimentally induced colon cancer. The radiochemical yield was observed to be 95.93 ± 1.09%. In silico docking studies revealed that [99mTc]Tc-GSH gets well accommodated in the binding pocket of gamma-glutamyl transpeptidase in comparable orientation with lowest estimated binding energy − 81.90. Toxicity assays i.e. 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and trypan blue exclusion assay showed that radiocomplex is non-toxic to HT 29 cells. In conclusion, in vitro and in vivo results indicated the [99mTc]Tc-GSH radiocomplex has tumor delineating features and also exhibits selectivity for colon tumor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18

Similar content being viewed by others

References

  1. Gulam W, Haseeb A (2006) Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinogen 5:14

    Article  Google Scholar 

  2. Demple B, Harrison L (1994) Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem 63:915–948

    Article  CAS  Google Scholar 

  3. Moller P, Wallin H (1998) Adduct formation, mutagenesis and nucleotide excision repair of DNA damage produced by reactive oxygen species and lipid peroxidation product. Mutat Res 410:271–290

    Article  CAS  Google Scholar 

  4. Shigenaga MK, Hagen TM, Ames BN (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91:10771–10778

  5. Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90:7915–7922

  6. Olinski R, Zastawny T, Budzbon J, Skokowski J, Zegarski W, Dizdaroglu M (1992) DNA base modifications in chromatin of human cancerous tissues. FEBS Lett 309:193–198

    Article  CAS  Google Scholar 

  7. A Bansal, CM Simon (2018) Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol 217(7):2291–2298

    Article  CAS  Google Scholar 

  8. Gupta RK, Patel AK, Shah N, Chaudhary AK, Jha UK, Yadav UC, Gupta PK, Pakuwal U (2014) Oxidative stress and antioxidants in disease and cancer: a review. Asian Pac J Cancer Prev 15:4405–4409

    Article  Google Scholar 

  9. Toyokuni S, Okamoto K, Yodoi J, Hiai H (1995) Persistent oxidative stress in cancer. FEBS Lett 358:1–3

    Article  CAS  Google Scholar 

  10. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: How are they linked? Free Radical Biol Med 49:1603–1616

    Article  CAS  Google Scholar 

  11. Meister A (1995) Glutathione metabolism. Methods in Enzymol 251:3–7

    Article  CAS  Google Scholar 

  12. Sies H (1999) Glutathione and its role in cellular functions. Free Rad Biol Med 27:916–921

    Article  Google Scholar 

  13. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (2004) Glutathione metabolism and its implications for health. J Nutr 134:489–492

    Article  CAS  Google Scholar 

  14. Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of atp-dependent transporters. Nat Rev Cancer 2:48–58

    Article  CAS  Google Scholar 

  15. Kaplowitz N, Aw TY, Ookhtens M (1985) The regulation of hepatic glutathione. Ann Rev Pharmacol Toxicol 25:715–744

    Article  CAS  Google Scholar 

  16. Zhang H, Forman HJ (2009) Redox regulation of gamma glutamyl transpeptidase. Am J Respir Cell Mol Biol 41:509–515

    Article  CAS  Google Scholar 

  17. Corti A, Franzini M, Paolicchi A, Pompella A (2010) Gamma-glutamyl transferase of cancer cells at the crossroads of tumor progression, drug resistance and drug targeting. Anticancer Res 30:1169–1181

    CAS  PubMed  Google Scholar 

  18. Bowen M, Orvig C (2008) 99 m-technetium carbohydrate conjugates as potential agents in molecular imaging. Chem Commun 41:5077–5091

    Article  Google Scholar 

  19. Wongso H, Zainuddin N, Iswahyudi I (2013) Biodistribution and imaging of 99mTc-glutathione radiopharmaceutical in white rats induced with cancer. Atom Indonesia 39(3):106–111

    Article  Google Scholar 

  20. Khurana H, Meena VK, Prakash S, Chuttani K, Chadha N, Jaswal A, Dhawan DK, Mishra AK, Hazari PP (2015) Preclinical evaluation of a potential GSH ester based PET/SPECT imaging probe DT(GSHMe)2 to detect Gamma Glutamyl Transferase over expressing tumors. PLoS ONE 10(7):e0134281

    Article  Google Scholar 

  21. Sadeghpour H, Alavi M, Shahedi M, Entezarmahdi SM, Sakhteman A, Kowalsky RJ, Falen SW (2014) Evaluation of radiochemical purities of some radiopharmaceuticals in Shiraz Namazi Teaching Hospital. Trends Pharmacol Sci 1(1):10–14

    Google Scholar 

  22. Zolle I (ed) (2007) 99mTc-phramaceutical preparation and quality control in nuclear medicine. ISBN-13: 978-3-540-33989-2$4. Springer, Berlin

  23. Pyka AL, Babuska M, Zachariasz MA (2006) A comparison of theoretical methods of calculation of partition coefficients for selected drugs. Acta poloniae pharmaceutica-Drug Res 63:159–167

    Google Scholar 

  24. Chadha VD, Goel, Dhawan DK (2011) Regulatory role of Zinc on the Biokinetics and Biodistribution of 65Zn during the Initiation of experimentally induced Colon cancer. Nutr Cancer 63(2):212–221

    Article  CAS  Google Scholar 

  25. Priyadarshani A, Chuttani K, Mittal G, Bhatnagar A (2010) Radiolabeling, biodistribution and gamma scintigraphy of noscapine hydrochloride in normal and polycystic ovary induced rats. J Ovarian Res 3:1–8

    Article  Google Scholar 

  26. Kumar RR, Dhawan DK, Chadha VD (2019) Development and initial characterization of 99mTc labeled N-acetyl neuraminic acid for its application in in-vivo imaging of cancer: a preclinical study. J Radioanal Nucl Chem 322:533–543

    Article  CAS  Google Scholar 

  27. Baba K, Moretti JL, Weinmann P, Senekowitsch-Schmidtke R, Ercan MT (1999) Tc-Glutathione Complex (Tc-GSH): labelling, chemical characterization and biodistribution in rats. Met-Based Drugs 6:865149

    Article  Google Scholar 

  28. Ercan MT, Bekdik CF, Sarizi T (1978) 99mTc-glutathione: labelling and distributionin rats. Int J Appl Rad Isot 29:697–698

    Article  CAS  Google Scholar 

  29. Saha GB (1996) The chemistry of Tc-99m-labeled radiopharmaceuticals. Albuq New Mexico 5:1

    Google Scholar 

  30. Dalhoff D, Ranek L, Mantoni M, Poulsen HE (1992) Glutathione treatment of hepatocellular carcinoma. Liver 12:341–343

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vijayta D. Chadha.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sidiq, S., Kumar, R.R., Passi, N.D. et al. Evaluation of 99mTc-labeled glutathione as a colon cancer targeting probe. J Radioanal Nucl Chem 327, 673–689 (2021). https://doi.org/10.1007/s10967-020-07563-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-020-07563-1

Keywords

Navigation