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Biodistribution and scintigraphic evaluation of 99mTc-Mannan complex

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

CITATION: 

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

Abstract

     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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