title: Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging.
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-(67)Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with (67)Ga-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-(67)Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-(67)Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad # 2001, Colonia Chamilpa, Cuernavaca, Morelos 62210, Mexico. ireneveba@gmail.com.
authors.forename: Irene
authors.initials: I
authors.lastname: Vergara
authors.affiliation: Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, Ciudad de México 14080, Mexico. erickcast14@gmail.com.
authors.forename: Erick Y
authors.initials: EY
authors.lastname: Castillo
authors.affiliation: Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, Ciudad de México 14080, Mexico. esau1708@gmail.com.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Romero-Piña
authors.affiliation: Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, Ciudad de México 14080, Mexico. itzel2606@gmail.com.
authors.forename: Itzel
authors.initials: I
authors.lastname: Torres-Viquez
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad # 2001, Colonia Chamilpa, Cuernavaca, Morelos 62210, Mexico. dashpame@gmail.com.
authors.forename: Dayanira
authors.initials: D
authors.lastname: Paniagua
authors.affiliation: Venom Immunochemistry, Pharmacology and Emergency Response (VIPER) Institute, University of Arizona College of Medicine, Tucson, AZ 85724, USA. boyer@viper.arizona.edu.
authors.forename: Leslie V
authors.initials: LV
authors.lastname: Boyer
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad # 2001, Colonia Chamilpa, Cuernavaca, Morelos 62210, Mexico. alagon@ibt.unam.mx.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Alagón
authors.affiliation: Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, Ciudad de México 14080, Mexico. medina@fisica.unam.mx.|Instituto de Física, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico. medina@fisica.unam.mx.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Medina
mesh_terms: D000818:Animals; D004546:Elapid Venoms / Q000737:chemistry*; D017815:Elapidae; D019786:Gadolinium DTPA / Q000737:chemistry / Q000493:pharmacokinetics*; D007928:Lethal Dose 50; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D051379:Mice; D057054:Molecular Imaging; D009498:Neurotoxins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000493:pharmacokinetics; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D014018:Tissue Distribution
chemical_list: D004546:Elapid Venoms; D009498:Neurotoxins; C053972:micrurus venom; D012710:Serum Albumin, Bovine; D019786:Gadolinium DTPA
keywords: coral snake; lymphatic absorption; molecular imaging; neurotoxin; radiolabeling