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Toxins 2016, 8(4), 85; doi:10.3390/toxins8040085

Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging

1
Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad # 2001, Colonia Chamilpa, Cuernavaca, Morelos 62210, Mexico
2
Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, Ciudad de México 14080, Mexico
3
Venom Immunochemistry, Pharmacology and Emergency Response (VIPER) Institute, University of Arizona College of Medicine, Tucson, AZ 85724, USA
4
Instituto de Física, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
*
Author to whom correspondence should be addressed.
Academic Editor: Wayne Hodgson
Received: 16 February 2016 / Revised: 16 March 2016 / Accepted: 16 March 2016 / Published: 26 March 2016
(This article belongs to the Section Animal Venoms)
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Abstract

The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx). The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA) and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50) and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming. View Full-Text
Keywords: coral snake; neurotoxin; lymphatic absorption; molecular imaging; radiolabeling coral snake; neurotoxin; lymphatic absorption; molecular imaging; radiolabeling
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Vergara, I.; Castillo, E.Y.; Romero-Piña, M.E.; Torres-Viquez, I.; Paniagua, D.; Boyer, L.V.; Alagón, A.; Medina, L.A. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging. Toxins 2016, 8, 85.

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