Evaluation of 99m Tc-MccJ25 peptide analog in mice bearing B16F10 melanoma tumor as a diagnostic radiotracer

Document Type: Original Article

Authors

1 Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

2 Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran

3 Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

4 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

Abstract

Objective(s): Despite recent advances in treatment modalities, cancer remains a major source of morbidity and mortality throughout the world. Currently, the development of sensitive and specific molecular imaging probes for early diagnosis of cancer is still a problematic challenge. Previous studies have been shown that some of the antimicrobial peptides (AMPs) exhibit a broad spectrum of cytotoxic activity against cancerous cells in addition to their antimicrobial activities. MicrocinJ25 (MccJ25) is an antimicrobial peptide that is produced by Escherichia coli (E. coli) strain. The aim of this study was to investigate the potential of a new peptide radiopharmaceutical derived from MccJ25 for diagnosis of melanoma tumor bearing C57BL/6 mice.
Methods: A 14 amino acid analog of MccJ25 was labeled with technetium-99m (99mTc) through hydrazinonicotinamide (HYNIC) chelator and tricine as coligand. In vivo tumor uptake and tissue distribution were evaluated. The in vivo biodistribution studies were determined in C57BL/6 mice bearing B16F10 tumor.
Results: The amount of non-peptide related 99mTc-impurities that measured by thin layer chromatography (TLC) did not exceed 5% of the total radioactivity. The in vitro binding to B16F10 cells was 30.73 ± 0.9% after 1 h incubation at 37°C, and saturation binding experiments showed good affinity for radio-complex (Kd=47.98±6.25 nM). The melanoma tumor was clearly visible up 1 h post-injection by gamma camera imaging.
Conclusion: The results showed that 99mTc-labeld peptide could be a promising candidate as a targeting radiopharmaceutical for melanoma tumor imaging in mice.

Keywords

Main Subjects


 

1. Arnold M, Karim-Kos HE, Coebergh JW, Byrnes G, Antilla A, Ferlay J, et al. Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory. Eur J Cancer. 2015;51(9):1164-87.

2. Thundimadathil J. Cancer treatment using peptides: current therapies and future prospects. J Amino Acids. 2012;2012:967347.

3. AL-Nahhas A, Fanti S. Radiolabelled peptides in diagnosis and therapy: an introduction. Eur J Nucl Med Mol Imaging. 2012;39(Suppl 1):S1-3.

4. Alauddin MM. Positron emission tomography (PET) imaging with 18F-based radiotracers. Am J Nucl Med Mol Imaging. 2012;2(1):55-76.

5. Petruzzi N, Shanthly N, Thakur M. Recent trends in soft-tissue infection imaging. Semin Nucl Med. 2009;39(2):115-23.

6. Manarang JC, Otteson DC, McDermott AM. Expression of antimicrobial peptides by uveal and cutaneous melanoma cells and investigation of their role in tumor cell migration and vasculogenic mimicry. Curr Eye Res. 2017;42(11):1474-81.

7. Felicio M R, Silva ON, Gonçalves S, Santos NC, Franco OL. Peptides with dual antimicrobial and anticancer activities. Front Chem. 2017;5:5.

8. Deslouches B, Di YP. Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications. Oncotarget. 2017; 8(28):46635-51.

9. Tonk M, Vilcinskas A, Rahnamaeian M. Insect antimicrobial peptides: potential tools for the prevention of skin cancer. Appl Microbiol Biotechnol. 2016;100(17):7397-405.

10. Lupetti A, Pauwels EK, Nibbering PH, Welling MM. 99mTc-Antimicrobial peptides: promising candidates for infection imaging. Q J Nucl Med. 2003;47(4):238-45.

11. Wilson KA, Kalkum M, Ottesen J, Yuzenkova J, Chait BT, Landick R, et al. Antimicrobial action of Mcc J25 variants against S. newport. J Am Chem Soc. 2003;125:12475-83.

12. Vincent PA, Delgado MA, Farias RN, Salomon RA. Inhibition of Salmonella enterica serovars by microcin J25. FEMS Microbiol Lett. 2004; 236(1):103-7.

13. Dupuy F, Morero R. Microcin J25 membrane interaction: selectivity toward gel phase. Biochim Biophys Acta. 2011;1808(6):1764-71.

14. Niklison-Chirou MV, Dupuy F, Pena LB, Gallego SM, Barreiro-Arcos ML, Avila C, et al. Microcin J25 triggers cytochrome c release through irreversible damage of mitochondrial proteins and lipids. Int J Biochem Cell Biol. 2009;42(2):273-81.

15. Pavlova O, Mukhopadhyay J, Sineva E, Ebright RH, Severinov K. Systematic structure-activity analysis of microcin J25. J Biol Chem. 2008;283(37):25589-95.

16. Mazaheri Tehrani M, Erfani M, Amirmozafari N, Nejadsattari T. Synthesis of a peptide derivative of microcin J25 and evaluation of antibacterial and biological activities. Iran J Pharm Res. 2019;In Press. 

17. Banerjee S, Pillai MR, Ramamoorthy N. Evolution of Tc-99m in diagnostic radiopharmaceuticals. Semin Nucl Med. 2001;31(4):260-77.

18. Babich JW, Solomon H, Pike MC, Kroon D, GrahamW, Abrams MJ. Technetium-99m-labeled hydrazino nicotin-amide derivatized chemotactic peptide analogs for imaging focal sites of bacterial infection. J Nucl Med. 1993;34(11):1964-74.

19. Rosenkranz AA, Slastnikova TA, Durymanov MO, Sobolev AS. Malignant melanoma and melanocortin 1 receptor. Biochemistry (Mosc). 2013;78(11):1228-37.

20. Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev. 2003;24(4):389-427.

21. Hoskin Dw, Ramamoorthy A. Studies on anticancer activities of antimicrobial peptides. Biochim Biophys Acta. 2008;1778(2):357-75.