Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma

Autores
Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Coutinho, Patricia De Souza; Henry, Leah; Lupu, Florea; Silasi Mansat, Robert; Ehernshaft, Marilyn; Mason, Ronald P.; Gomez-Mejiba, Sandra Esther; Ramirez, Dario
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Free radicals play a major role in gliomas. By combining immuno-spin-trapping (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine serum albumin (BSA)–Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)–biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected the presence of anti-DMPO adducts by either a significant sustained increase (p < 0.001) in MR signal intensity or a significant decrease (p < 0.001) in T1 relaxation, measured as %T1 change. In vitro assessment of the anti-DMPO probe indicated a significant decrease (p < 0.0001) in T1 relaxation in GL261 cells that were oxidatively stressed with hydrogen peroxide, compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised brain tissues. As a negative control a non-specific IgG antibody covalently bound to the albumin–Gd-DTPA–biotin construct was used. DMPO adducts were also confirmed in tumor tissue from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas were found to have significantly increased malondialdehyde (MDA) protein adducts (p < 0.001) and 3-nitrotyrosine (3-NT) (p < 0.05) compared to normal mouse brain tissue, indicating increased oxidized lipids and proteins, respectively. Co-localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also observed. This is the first report regarding the detection of in vivo levels of free radicals from a glioma model.
Fil: Towner, Rheal A.. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Smith, Nataliya. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Saunders, Debra. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Coutinho, Patricia De Souza. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Henry, Leah. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Lupu, Florea. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Silasi Mansat, Robert. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Ehernshaft, Marilyn. National Institute of Environmental Health Sciences. Laboratory of Toxicology and Pharmacology; Estados Unidos
Fil: Mason, Ronald P.. National Institute of Environmental Health Sciences. Laboratory of Toxicology and Pharmacology ; Estados Unidos
Fil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
Glioma
Free Radical
Immuno-Spin Trapping
Mri
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4362
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4362
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 gliomaTowner, Rheal A.Smith, NataliyaSaunders, DebraCoutinho, Patricia De SouzaHenry, LeahLupu, FloreaSilasi Mansat, RobertEhernshaft, MarilynMason, Ronald P.Gomez-Mejiba, Sandra EstherRamirez, DarioGliomaFree RadicalImmuno-Spin TrappingMrihttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Free radicals play a major role in gliomas. By combining immuno-spin-trapping (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine serum albumin (BSA)–Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)–biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected the presence of anti-DMPO adducts by either a significant sustained increase (p < 0.001) in MR signal intensity or a significant decrease (p < 0.001) in T1 relaxation, measured as %T1 change. In vitro assessment of the anti-DMPO probe indicated a significant decrease (p < 0.0001) in T1 relaxation in GL261 cells that were oxidatively stressed with hydrogen peroxide, compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised brain tissues. As a negative control a non-specific IgG antibody covalently bound to the albumin–Gd-DTPA–biotin construct was used. DMPO adducts were also confirmed in tumor tissue from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas were found to have significantly increased malondialdehyde (MDA) protein adducts (p < 0.001) and 3-nitrotyrosine (3-NT) (p < 0.05) compared to normal mouse brain tissue, indicating increased oxidized lipids and proteins, respectively. Co-localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also observed. This is the first report regarding the detection of in vivo levels of free radicals from a glioma model.Fil: Towner, Rheal A.. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados UnidosFil: Smith, Nataliya. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados UnidosFil: Saunders, Debra. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados UnidosFil: Coutinho, Patricia De Souza. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados UnidosFil: Henry, Leah. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados UnidosFil: Lupu, Florea. Oklahoma Medical Research Foundation; Estados UnidosFil: Silasi Mansat, Robert. Oklahoma Medical Research Foundation; Estados UnidosFil: Ehernshaft, Marilyn. National Institute of Environmental Health Sciences. Laboratory of Toxicology and Pharmacology; Estados UnidosFil: Mason, Ronald P.. National Institute of Environmental Health Sciences. Laboratory of Toxicology and Pharmacology ; Estados UnidosFil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaElsevier2013-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4362Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Coutinho, Patricia De Souza; Henry, Leah; et al.; Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma; Elsevier; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1832; 12; 12-2013; 2153-21610925-4439enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S092544391300269Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbadis.2013.08.004info:eu-repo/semantics/altIdentifier/issn/0925-4439info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:43Zoai:ri.conicet.gov.ar:11336/4362instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:09:43.7CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma
title Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma
spellingShingle Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma
Towner, Rheal A.
Glioma
Free Radical
Immuno-Spin Trapping
Mri
title_short Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma
title_full Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma
title_fullStr Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma
title_full_unstemmed Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma
title_sort Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma
dc.creator.none.fl_str_mv Towner, Rheal A.
Smith, Nataliya
Saunders, Debra
Coutinho, Patricia De Souza
Henry, Leah
Lupu, Florea
Silasi Mansat, Robert
Ehernshaft, Marilyn
Mason, Ronald P.
Gomez-Mejiba, Sandra Esther
Ramirez, Dario
author Towner, Rheal A.
author_facet Towner, Rheal A.
Smith, Nataliya
Saunders, Debra
Coutinho, Patricia De Souza
Henry, Leah
Lupu, Florea
Silasi Mansat, Robert
Ehernshaft, Marilyn
Mason, Ronald P.
Gomez-Mejiba, Sandra Esther
Ramirez, Dario
author_role author
author2 Smith, Nataliya
Saunders, Debra
Coutinho, Patricia De Souza
Henry, Leah
Lupu, Florea
Silasi Mansat, Robert
Ehernshaft, Marilyn
Mason, Ronald P.
Gomez-Mejiba, Sandra Esther
Ramirez, Dario
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glioma
Free Radical
Immuno-Spin Trapping
Mri
topic Glioma
Free Radical
Immuno-Spin Trapping
Mri
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Free radicals play a major role in gliomas. By combining immuno-spin-trapping (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine serum albumin (BSA)–Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)–biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected the presence of anti-DMPO adducts by either a significant sustained increase (p < 0.001) in MR signal intensity or a significant decrease (p < 0.001) in T1 relaxation, measured as %T1 change. In vitro assessment of the anti-DMPO probe indicated a significant decrease (p < 0.0001) in T1 relaxation in GL261 cells that were oxidatively stressed with hydrogen peroxide, compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised brain tissues. As a negative control a non-specific IgG antibody covalently bound to the albumin–Gd-DTPA–biotin construct was used. DMPO adducts were also confirmed in tumor tissue from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas were found to have significantly increased malondialdehyde (MDA) protein adducts (p < 0.001) and 3-nitrotyrosine (3-NT) (p < 0.05) compared to normal mouse brain tissue, indicating increased oxidized lipids and proteins, respectively. Co-localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also observed. This is the first report regarding the detection of in vivo levels of free radicals from a glioma model.
Fil: Towner, Rheal A.. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Smith, Nataliya. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Saunders, Debra. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Coutinho, Patricia De Souza. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Henry, Leah. Oklahoma Health Sciences Center. Advanced Magnetic Resonance Center; Estados Unidos
Fil: Lupu, Florea. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Silasi Mansat, Robert. Oklahoma Medical Research Foundation; Estados Unidos
Fil: Ehernshaft, Marilyn. National Institute of Environmental Health Sciences. Laboratory of Toxicology and Pharmacology; Estados Unidos
Fil: Mason, Ronald P.. National Institute of Environmental Health Sciences. Laboratory of Toxicology and Pharmacology ; Estados Unidos
Fil: Gomez-Mejiba, Sandra Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Ramirez, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description Free radicals play a major role in gliomas. By combining immuno-spin-trapping (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine serum albumin (BSA)–Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)–biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected the presence of anti-DMPO adducts by either a significant sustained increase (p < 0.001) in MR signal intensity or a significant decrease (p < 0.001) in T1 relaxation, measured as %T1 change. In vitro assessment of the anti-DMPO probe indicated a significant decrease (p < 0.0001) in T1 relaxation in GL261 cells that were oxidatively stressed with hydrogen peroxide, compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised brain tissues. As a negative control a non-specific IgG antibody covalently bound to the albumin–Gd-DTPA–biotin construct was used. DMPO adducts were also confirmed in tumor tissue from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas were found to have significantly increased malondialdehyde (MDA) protein adducts (p < 0.001) and 3-nitrotyrosine (3-NT) (p < 0.05) compared to normal mouse brain tissue, indicating increased oxidized lipids and proteins, respectively. Co-localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also observed. This is the first report regarding the detection of in vivo levels of free radicals from a glioma model.
publishDate 2013
dc.date.none.fl_str_mv 2013-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/4362
Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Coutinho, Patricia De Souza; Henry, Leah; et al.; Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma; Elsevier; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1832; 12; 12-2013; 2153-2161
0925-4439
url http://hdl.handle.net/11336/4362
identifier_str_mv Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Coutinho, Patricia De Souza; Henry, Leah; et al.; Combined molecular MRI and immuno-spin trapping for in vivo detection of free radicals in orthotopic mouse GL261 glioma; Elsevier; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1832; 12; 12-2013; 2153-2161
0925-4439
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S092544391300269X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbadis.2013.08.004
info:eu-repo/semantics/altIdentifier/issn/0925-4439
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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