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Synthesis and biological evaluation of 99mTc-ECF: a new ethionamide derivative for tuberculosis diagnosis

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Abstract

In this work we propose a technetium-99m-labeled derivative from Ethionamide (ETH), further referred to as 99mTc-ECF for tuberculosis diagnosis. The biological features of this radioactive agent have been studied. The 2-ethylpyridine-4-carbothioamide-ferrocène (ECF) was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that 99mTc-ECF is obtained with high radiolabelling yield (>90 %). Radiochemical analysis of 99mTc-ECF revealed that the molecule was efficiently labeled with a little free remaining pertechnetate. Only 1–2 % of the tracer was leached out from the complex at 24 h when incubated in serum at 37 °C which confirmed its high stability. The sensitivity test of ECF showed that the group of grafted ferrocenyl does not seem to have largely altered the active site of the molecule. In-vitro investigations were conducted using BCG (Bacille Calmette-Guérin) as analogue of Mycobacterium Tuberculosis and Listeria Monocytogenes as negative control. It was proved that for BCG, ECF has kept the bacteriostatic properties of the parent compound (ETH). In physiological conditions, the measured up-take of the tracer with live bacteria was about 24.1 and 7.1 % for BCG and Listeria Monocytogenese, respectively. The comparison of the 99mTc-ECF accumulation at sites of BCG infected animals, which is expressed as target-to-non-target ratio (found to be equal to 2.15) with other radiotracers was discussed. This allowed us to consider that 99mTc-ECF could be a reasonable radiotracer for mycobacterial infections. Obtained results were good and encourage to undergo a similar labeling for the Mycobacterium tuberculosis as perspective of this work.

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References

  1. Yurt LF, Durkan K, Unak P (2008) Preparation, quality control and stability of 99 mTc-cefuroxime axetil. J Radioanal Nucl Chem 275:161–164

    Article  Google Scholar 

  2. Peters AM (1994) The utility of [99mTc]-HMPAO-leucocytes for imaging infection. Semin Nucl Med 24:110–127

    Article  CAS  Google Scholar 

  3. Datz FL (1994) Indium-111-labelled leucocytes for the detection of infection: current status. Semin Nucl Med 24:92–109

    Article  CAS  Google Scholar 

  4. Cook PS, Datz FL, Disbro MA et al (1984) Pulmonary uptake in indium-111-leucocyte imaging. Clinical significance in patient with suspected occult infections. Radiology 150:557–561

    CAS  Google Scholar 

  5. Vinjamuri S, Solanki KK (1996) Comparison of Tc-99m infecton imaging with radiolabeled white cell imaging in the evaluation of bacterial infection. Lancet 346:233–235

    Article  Google Scholar 

  6. Hall AV, Solanki KK, Vinjamuri S et al (1998) Evaluation of the efficacy of “99mTc-infecton”: a novel agent for detecting sites of infection. J Clin Pathol 51:215–219

    Article  CAS  Google Scholar 

  7. Britton KE, Wareham DW, Dass S, Solanki KK (2002) Imaging bacterial infection with 99mTc-ciprofloxacin. J Clin Pathol 55:817–823

    Article  CAS  Google Scholar 

  8. Bakheet SM, Powe J, Kandil A, Ezzat A, Rostom A, Amartey J (2000) F-18 FDG uptake in breast infection and inflammation (1953). Clin Nucl Med 25:100–103

    Article  CAS  Google Scholar 

  9. Cheery SR (2001) Fundamentals of positron emission tomography and application in preclinical drug development. J Clin Pharmacol 4:482–491

    Article  Google Scholar 

  10. Bhatnagar A, Sharma R, Gupta S, Singh AK, Soni NL, Rawat H (1999) Possible role of 99mTc-Dextran (99mTc-DX) in detection of occult small intestinal lesion. Indian J Nucl Med 14:30–32

    Google Scholar 

  11. Bhatnagar A, Jain CM, Singh AK, Kashyap R, Gupta A, Chopra MK, Swaroop K (1999) A comparative study of 99mTcinfecton, 99mTc-human immunoglobulin G and 99mTc-Dextran in tubercular bone disease. Indian J Nucl Med 14:10–16

    Google Scholar 

  12. Singh AK, Bharadwaj N, Singh T, Kashyap R et al (2002) “Diagnobact” single vial cold kit of 99mTc-ciprofloxacin ready for multicentric trails. Indian J Nucl Med 17:16

    Google Scholar 

  13. Beckerman C (1988) Gallium-67 scanning in clinical evaluation of human immunodeficiency virus infection: indications and limitations. Semin Nucl Med 18:273

    Article  Google Scholar 

  14. Buscombe JR, Lui D, Ensing G, Jong D, Ell PJ (1990) 99mTc human immunoglobulin first result of new agent for localization of infection and inflammation. Eur J Nucl Med 16:649–655

    Article  CAS  Google Scholar 

  15. Onsel C, Sonmezoglu K, Camsari G et al (1996) Techetium-99m MIBI scintigraphy in pulmonary tuberculosis. Indian J Nucl Med 37:233–238

    CAS  Google Scholar 

  16. Degirmenci KO, Cirak KA, Akpinar O, Halilcolar H, Durak H (1998) 99mTc-tetrofosmin scintigraphy in pulmonary tuberculosis. J Nucl Med 39:2116–2120

    CAS  Google Scholar 

  17. Essouissi I, Malek SN, Bernard S, Guizani S, Mejri N, Barc C, Ben hamouda S, Asmi A, Saidi M (2012) 99mTc-N-IFC: a new Isoniazid derivative for Mycobacterium diagnostic. Radiochim Acta 99:1–9

    Google Scholar 

  18. Alberto R (2005) In: Jaouen G (ed) Radiopharmaceuticals. Weinheim: Wiley-VCH

  19. Schibli R, Schubiger AP (2002) Current use and future potential of organometallic radiopharmaceuticals. Eur J Nucl Med Mol Imaging 29:1529–1542

    Article  CAS  Google Scholar 

  20. Alberto R (2007) The particular role of radiopharmacy within bioorganometallic chemistry. J Organomet Chem 692:1179–1186

    Article  CAS  Google Scholar 

  21. Arimoto S, Haven AC (1955) Derivatives of dicyclopentadienyliron. J Am Chem Soc 77:6295–6297

    Article  CAS  Google Scholar 

  22. Lorkowski HJ, Pannier R, Wende A (1967) Über Ferrocenderivate. VIII. Die Darstellung von monomeren und polymeren Ferrocenylenoxadiazolen. J Prakt Chem 35:149–158

    Article  CAS  Google Scholar 

  23. Saïdi M, Seifert S, Kretzschmar M, Bergmann R, Pietzsch HJ (2004) Cyclopentadienyl tricarbonyl complexes of 99mTc for the in vivo imaging of the serotonin 5-HT1A receptor in the brain. J Organomet Chem 689:4739–4744

    Article  Google Scholar 

  24. Rusckowski M, Gupta S, Liu G, Dou S, Hnatowich DJ (2004) Investigation of a 99m-Tc-labelled bacteriophages as a potential infection-specific imaging agent. J Nucl Med 45:1201–1208

    CAS  Google Scholar 

  25. Belhadj-Tab H, Coulais Y, Cros G, Darbieu MH, Tafani JAM, Fabre J (1996) Technetium labeling of Bi, Tri and tetradentate ligands derived from 2 aminocyclopentene-1-dithiocarboxylic acid: characterization and biodistribution of their oxo and nitrido 99mTechnetium complexes. Nucl Med Biol 23:353–357

    Article  Google Scholar 

  26. Ephraim EP, Carl J, Terry S, Michael JW, John AK (2006) Synthesis and biological evaluation of a nonsteroidal bromine-76-labeled androgen receptor ligand 3-[76Br]bromo-hydroxyflutamide. Nucl Med Biol 33:705–713

    Article  Google Scholar 

  27. Madigan M, Martinko J (2005) Brock Biology of Microorganisms, 11th edn. Prentice Hall, Upper Saddle River

    Google Scholar 

  28. Felease (2006) Euroguide: on the accommodation and care of animals used for experimental and other scientific purpose. British library

  29. Singh AK, Verma J, Bhatnagar A, Sen S, Bose M (2003) Tc-99m isoniazid: a specific agent for diagnosis of tuberculosis. World J Nucl Med 2:292–305

    Google Scholar 

  30. Wenzel M (2006) Tc-99m labeling of cymantrene-analogues with different substituents. A new approach to Tc-99m radiodiagnostics. J Label Compd Radiopharm 31:641–650

    Article  Google Scholar 

  31. Meral TE, Tülin A, Isil S, Ünsal (1992) Evaluation of 99mTc erythromycin and 99mTc-streptomycin sulphate for the visualization of inflammatory lesions. Nucl Med Biol 19:803–806

    Google Scholar 

  32. Roohi S, Mushtaq A, Jehangir M, Malik S (2006) A Synthesis, quality control and biodistribution of 99mTc-Kanamycin. J Radioanal Nucl Chem 267:561–566

    Article  CAS  Google Scholar 

  33. Essouissi I, Ghali W, Saidi M (2010) Synthesis and evaluation of 99mTc-N-sulfanilamide ferrocene carboxamide as bacterial infections detector. Nucl Med Biol 37:821–829

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the researchers of the mycobacterium laboratory of the Pasteur Institute (Tunisia) for their cooperation and help with some experiments carried out through this work. We would also thank the anonymous reviewers for helping us to improve significantly the quality of the text.

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Authors and Affiliations

  1. Radiopharmaceutical Unit, National Centre of Sciences and Nuclear Technologies (CNSTN), 2020, Sidi Thabet, Tunisia

    Imen Essouissi, Nadia Malek Saied, Najoua Mejri, Sihem Guizani & Mouldi Saidi

  2. Microbiology Unit, National Centre of Sciences and Nuclear Technologies, Sidi Thabet, Tunisia

    Hadeer Lazim

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  1. Imen Essouissi
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Correspondence to Imen Essouissi.

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Essouissi, I., Saied, N.M., Mejri, N. et al. Synthesis and biological evaluation of 99mTc-ECF: a new ethionamide derivative for tuberculosis diagnosis. J Radioanal Nucl Chem 300, 987–996 (2014). https://doi.org/10.1007/s10967-014-3059-4

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  • DOI: https://doi.org/10.1007/s10967-014-3059-4

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