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Biodistribution and scintigraphic evaluation of 99mTc-Mannan complex

DISCOVERIES (ISSN 2359-7232), 2016, July-September issue


Sanguri S, Gupta D, Singh T, Singh AK. Biodistribution and scintigraphic evaluation of 99mTc-Mannan complex. Discoveries 2016, Jul-Sep; 4(3): e65 DOI: 10.15190/d.2016.12

Submitted: September 23, 2016; Revised: September 30, 2016; Accepted: September 30, 2016; Published: October 1, 2016;

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Biodistribution and scintigraphic evaluation of 99mTc-Mannan complex

Sweta Sanguri, Damodar Gupta*, Thakuri Singh, Ajay K. Singh

Division of Metabolic Cell Signalling Research, Institute of Nuclear Medicine and Allied Sciences, Defence Reseach and Development Organization (DRDO), Brig SK Mazumdar Marg, Timarpur, Delhi 110054, India

*Correspondence toDamodar Gupta, PhD, Division of Metabolic Cell Signaling Research, INMAS, DRDO, Delhi 110054, India; Emails: damodar@inmas.drdo.in and damodar.gupta@gmail.com


     Technetium-99m (99mTc) is extensively used in nuclear medicine, mostly used to label radiopharmaceuticals and in radio diagnostics. In the present study, we directly radiolabeled mannan with 99mTc by using Tin(II) Chloride Dihydrate (SnCl2·2H2O) as a reducing agent. Mannan, a TLR agonist is a complex carbohydrate identified as a potential modulator of biological effects of ionizing radiation, both in vitro and in vivo, in our laboratory. Under in vivo conditions mannan modulates radiation response when administered through either oral or parenteral routes. The present study aims to understand the pharmacologic biodistribution of the 99mTc-mannan complex in mice (via oral, i.p. and i.v. routes) using non-invasive scintigraphic imaging and invasive radiometry. Qualitative and quantitative analysis of 99mTc-mannan complex was performed by ITLC-SG, ascending paper chromatography. Radio-complexation efficiency of >98% was consistently achieved with hydrolyzed reduced Tc-99m being 1-2%. We confirmed stability of complex in saline and serum up to 24 h at room temperature. Biodistribution studies were performed using the above radiocomplex in BALB/c mice and 99mTc-mannan complex was administered though oral, i.p. and i.v. routes. To our expectations, most of the radioactivity accumulated in stomach and small intestine in mice with oral administration, along with insignificant activity in the remaining studied organs. It suggests that 99mTc-mannan complex did not get absorbed from the gut and was removed as such in the fecal material. On the contrary, i.p. and i.v administration of mannan resulted in significant accumulation of the 99mTc-mannan complex in kidney, liver, intestine, lungs, spleen, bone marrow, blood and heart, at both 1 h and 4 h after i.v. administration. The remaining organs (stomach, testis, skin, and muscles) showed lower accumulation of the 99mTc-mannan complex. 99mTc-mannan complex was adminstered (i.v.) in New Zealand white rabbits and it was evident from the scintigraphic images that mannan cleared very rapidly from the administration site and reached into systemic circulation. No activity in the thyroid, salivary gland, or gastric mucosa suggests an insignificant amount of free pertechnetate in the 99mTc-complex preparation, further confirming the in vivo stability of the radiolabeled mannan complex. Significant amount of radioactivity in liver, intestine and kidneys suggests hepatobiliary as well as renal routes of clearance. The bio-availability of the complex varies with the route of administration. An entirely different biodistribution pattern exists when the same molecule is administered through oral or parenteral route. Our study is the first step towards a better understanding of the mechanisms involved in radiation modulation offered by mannan administration, in vivo.

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1. Richards P, Tucker WD, Srivastava SC. Technetium-99m: an historical perspective. Int J Appl Radiat Isot 1982 Oct; 33(10): 793-799.

2. Mamedov MK, Akhmedova IN. [Restoration of the activity of an antibody-peroxidase conjugate using an erythrocyte lysate]. Lab Delo 1989; (12): 29-30.

3. Smith EM. Properties, Uses, Radiochemical Purity and Calibration of Tc-99m. J Nucl Med 1964 Nov; 5: 871-882.

4. Rennen HJ, van Eerd JE, Oyen WJ, Corstens FH, Edwards DS, Boerman OC. Effects of coligand variation on the in vivo characteristics of Tc-99m-labeled interleukin-8 in detection of infection. Bioconjug Chem 2002 Mar-Apr; 13(2): 370-377.

5. Edwards DS, Liu S, Ziegler MC, Harris AR, Crocker AC, Heminway SJ, et al. RP463: a stabilized technetium-99m complex of a hydrazino nicotinamide derivatized chemotactic peptide for infection imaging. Bioconjug Chem 1999 Sep-Oct; 10(5): 884-891.

6. Lambrecht FY. Evaluation of (9)(9)(m)Tc-labeled antibiotics for infection detection. Ann Nucl Med 2011 Jan; 25(1): 1-6.

7. Senocak O, Degirmenci B, Ozdogan O, Akalin E, Arslan G, Kaner B, et al. Technetium-99m human immunoglobulin scintigraphy in patients with adhesive capsulitis: a correlative study with bone scintigraphy. Ann Nucl Med 2002 Jun; 16(4): 243-248.

8. Selander B, Martensson U, Weintraub A, Holmstrom E, Matsushita M, Thiel S, et al. Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. J Clin Invest 2006 May; 116(5): 1425-1434.

9. Bozkurt M, Kucukyilmaz K, Catli AU, Cinar M, Bintas E, Coven F. Performance, egg quality, and 

immune response of laying hens fed diets supplemented with mannan-oligosaccharide or an essential oil mixture under moderate and hot environmental conditions. Poult Sci 2012 Jun; 91(6): 1379-1386.

10. Halas V, Nochta I. Mannan Oligosaccharides in Nursery Pig Nutrition and Their Potential Mode of Action. Animals (Basel) 2012; 2(2): 261-274.

11. Razeghi Mansour M, Akrami R, Ghobadi SH, Amani Denji K, Ezatrahimi N, Gharaei A. Effect of dietary mannan oligosaccharide (MOS) on growth performance, survival, body composition, and some hematological parameters in giant sturgeon juvenile (Huso huso Linnaeus, 1754). Fish Physiol Biochem 2012 Jun; 38(3): 829-835.

12. Yamabhai M, Sak-Ubol S, Srila W, Haltrich D. Mannan biotechnology: from biofuels to health. Crit Rev Biotechnol 2016; 36(1): 32-42.

13. Hutsko SL, Meizlisch K, Wick M, Lilburn MS. Early intestinal development and mucin transcription in the young poult with probiotic and mannan oligosaccharide prebiotic supplementation. Poult Sci 2016 Mar 4.

14. Santos EG, Costa FG, Silva JH, Martins TD, Figueiredo-Lima DF, Macari M, et al. Protective effect of mannan oligosaccharides against early colonization by Salmonella Enteritidis in chicks is improved by higher dietary threonine levels. J Appl Microbiol 2013 Apr; 114(4): 1158-1165.

15. Torrecillas S, Montero D, Caballero MJ, Robaina L, Zamorano MJ, Sweetman J, et al. Effects of dietary concentrated mannan oligosaccharides supplementation on growth, gut mucosal immune system and liver lipid metabolism of European sea bass (Dicentrarchus labrax) juveniles. Fish Shellfish Immunol 2015 Feb; 42(2): 508-516.

16. Momeni-Moghaddam P, Keyvanshokooh S, Ziaei-Nejad S, Parviz Salati A, Pasha-Zanoosi H. Effects of mannan oligosaccharide supplementation on growth, some immune responses and gut lactic acid bacteria of common carp (Cyprinus Carpio) fingerlings. Vet Res Forum 2015 Summer; 6(3): 239-244.

17. Zhang J, Liu Y, Tian L, Yang H, Liang G, Xu D. Effects of dietary mannan oligosaccharide on growth performance, gut morphology and stress tolerance of juvenile Pacific white shrimp, Litopenaeus vannamei. Fish Shellfish Immunol 2012 Oct; 33(4): 1027-1032.

18. Madrigal-Santillan E, Alvarez-Gonzalez I, Marquez-Marquez R, Velazquez-Guadarrama N, Madrigal-Bujaidar E. Inhibitory effect of mannan on the toxicity produced in mice fed aflatoxin B1 contaminated corn. Arch Environ Contam Toxicol 2007 Oct; 53(3): 466-472.

19. Madrigal-Santillan E, Morales-Gonzalez JA, Sanchez-Gutierrez M, Reyes-Arellano A, Madrigal-Bujaidar E. Investigation on the protective effect of alpha-mannan against the DNA damage induced by aflatoxin B(1)in mouse hepatocytes. Int J Mol Sci 2009 Feb; 10(2): 395-406.

20. Fernandez F, Hinton M, Van Gils B. Dietary mannan-oligosaccharides and their effect on chicken caecal microflora in relation to Salmonella Enteritidis colonization. Avian Pathol 2002 Feb; 31(1): 49-58.

21. Jahanian R, Ashnagar M. Effect of dietary supplementation of mannan-oligosaccharides on performance, blood metabolites, ileal nutrient digestibility, and gut microflora in Escherichia coli-challenged laying hens. Poult Sci 2015 Sep; 94(9): 2165-2172.

22. Cuskin F, Lowe EC, Temple MJ, Zhu Y, Cameron EA, Pudlo NA, et al. Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism. Nature 2015 Jan 8; 517(7533): 165-169.

23. Opanasopit P, Shirashi K, Nishikawa M, Yamashita F, Takakura Y, Hashida M. In vivo recognition of mannosylated proteins by hepatic mannose receptors and mannan-binding protein. Am J Physiol Gastrointest Liver Physiol 2001 May; 280(5): G879-889.

24. Taylor ME, Bezouska K, Drickamer K. Contribution to ligand binding by multiple carbohydrate-recognition domains in the macrophage mannose receptor. J Biol Chem 1992 Jan 25; 267(3): 1719-1726.

25. Schreiber S, Blum JS, Stenson WF, MacDermott RP, Stahl PD, Teitelbaum SL, et al. Monomeric IgG2a promotes maturation of bone-marrow macrophages and expression of the mannose receptor. Proc Natl Acad Sci U S A 1991 Mar 1; 88(5): 1616-1620.

26. Schreiber S, Perkins SL, Teitelbaum SL, Chappel J, Stahl PD, Blum JS. Regulation of mouse bone marrow macrophage mannose receptor expression and activation by prostaglandin E and IFN-gamma. J Immunol 1993 Nov 1; 151(9): 4973-4981.

27. Kogelberg H, Tolner B, Sharma SK, Lowdell MW, Qureshi U, Robson M, et al. Clearance mechanism of a mannosylated antibody-enzyme fusion protein used in experimental cancer therapy. Glycobiology 2007 Jan; 17(1): 36-45.

28. Herpers BL, Endeman H, de Jong BA, de Jongh BM, Grutters JC, Biesma DH, et al. Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes. Clin Exp Immunol 2009 Jun; 156(3): 488-494.

29. Saevarsdottir S, Vikingsdottir T, Valdimarsson H. The potential role of mannan-binding lectin in the clearance of self-components including immune complexes. Scand J Immunol 2004 Jul-Aug; 60(1-2): 23-29.

30. Kappe R, Muller J. Rapid clearance of Candida albicans mannan antigens by liver and spleen in contrast to prolonged circulation of Cryptococcus neoformans antigens. J Clin Microbiol 1991 Aug; 29(8): 1665-1669.

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