Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model

Autores
Geninatti Crich, Simonetta; Cutrin, Juan Carlos; Lanzardo, Stefania; Conti, Laura; Kálmán, Ferenc K.; Szabó, Ibolya; Lago, Néstor Rubén; Iolascon, Achille; Aime, Silvio
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mn-Apo is a highly sensitive MRI contrast agent consisting of ca. 1000 manganese atoms entrapped in the inner cavity of apoferritin. Part of the metallic payload is in the form of Mn2+ ions that endow the nano-sized system with a very high relaxivity that can be exploited to detect hepatocellular carcinoma in mice. Cellular studies showed that Mn-Apo is readily taken up by normal hepatocytes via the ferritin transporting route. Conversely, hepatoma cells (HTC) displayed a markedly reduced ability to entrap Mn-Apo from the culture medium. The i.v. administration of Mn-Apo into C57BL/6 J mice resulted in a marked liver tissue hyperintensity in T1-weighted MR image 20 min after injection. When injected into HBV-tg transgenic mice that spontaneously develop hepatocellular carcinoma (HCC), Mn-Apo allowed a clear delineation of healthy liver tissue and tumor lesions as hyperintense and hypointense T1-weighted MR images, respectively. Immunohistochemistry analysis correlated Mn-Apo cellular uptake to SCARA5 receptor expression. When the MRI contrast induced by Mn-Apo was compared with that induced by Gd–BOPTA (a commercial contrast agent known to enter mouse hepatocytes through organic anion transporters) it was found that only some of the lesions were detected by both agents while others could only be visualized by one of the two. These results suggest that Mn-Apo may be useful to detect otherwise invisible lesions and that the extent of its uptake directly reports the expression/regulation of SCARA5 receptors. Mn-Apo contrastenhanced MR images may therefore contribute to improving HCC lesion detection and characterization.
Fil: Geninatti Crich, Simonetta. University of Turin; Italia
Fil: Cutrin, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Lanzardo, Stefania. University of Turin; Italia
Fil: Conti, Laura. University of Turin; Italia
Fil: Kálmán, Ferenc K.. University of Turin; Italia
Fil: Szabó, Ibolya. University of Turin; Italia
Fil: Lago, Néstor Rubén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentina
Fil: Iolascon, Achille. University of Naples; Italia
Fil: Aime, Silvio. University of Turin; Italia
Materia
hepatocarcinoma
raton transgenico
MRI
apoferritina
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/273058
Acceder
id CONICETDig_059f84425bc0a6a4979e7e2c0487ad23
oai_identifier_str oai:ri.conicet.gov.ar:11336/273058
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse modelGeninatti Crich, SimonettaCutrin, Juan CarlosLanzardo, StefaniaConti, LauraKálmán, Ferenc K.Szabó, IbolyaLago, Néstor RubénIolascon, AchilleAime, Silviohepatocarcinomaraton transgenicoMRIapoferritinahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Mn-Apo is a highly sensitive MRI contrast agent consisting of ca. 1000 manganese atoms entrapped in the inner cavity of apoferritin. Part of the metallic payload is in the form of Mn2+ ions that endow the nano-sized system with a very high relaxivity that can be exploited to detect hepatocellular carcinoma in mice. Cellular studies showed that Mn-Apo is readily taken up by normal hepatocytes via the ferritin transporting route. Conversely, hepatoma cells (HTC) displayed a markedly reduced ability to entrap Mn-Apo from the culture medium. The i.v. administration of Mn-Apo into C57BL/6 J mice resulted in a marked liver tissue hyperintensity in T1-weighted MR image 20 min after injection. When injected into HBV-tg transgenic mice that spontaneously develop hepatocellular carcinoma (HCC), Mn-Apo allowed a clear delineation of healthy liver tissue and tumor lesions as hyperintense and hypointense T1-weighted MR images, respectively. Immunohistochemistry analysis correlated Mn-Apo cellular uptake to SCARA5 receptor expression. When the MRI contrast induced by Mn-Apo was compared with that induced by Gd–BOPTA (a commercial contrast agent known to enter mouse hepatocytes through organic anion transporters) it was found that only some of the lesions were detected by both agents while others could only be visualized by one of the two. These results suggest that Mn-Apo may be useful to detect otherwise invisible lesions and that the extent of its uptake directly reports the expression/regulation of SCARA5 receptors. Mn-Apo contrastenhanced MR images may therefore contribute to improving HCC lesion detection and characterization.Fil: Geninatti Crich, Simonetta. University of Turin; ItaliaFil: Cutrin, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Lanzardo, Stefania. University of Turin; ItaliaFil: Conti, Laura. University of Turin; ItaliaFil: Kálmán, Ferenc K.. University of Turin; ItaliaFil: Szabó, Ibolya. University of Turin; ItaliaFil: Lago, Néstor Rubén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Iolascon, Achille. University of Naples; ItaliaFil: Aime, Silvio. University of Turin; ItaliaJohn Wiley & Sons Ltd2012-04info: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/11336/273058Geninatti Crich, Simonetta; Cutrin, Juan Carlos; Lanzardo, Stefania; Conti, Laura; Kálmán, Ferenc K.; et al.; Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model; John Wiley & Sons Ltd; Contrast Media & Molecular Imaging; 7; 3; 4-2012; 281-2881555-4309CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmmi.492info:eu-repo/semantics/altIdentifier/doi/10.1002/cmmi.492info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:26:51Zoai:ri.conicet.gov.ar:11336/273058instacron: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:34982025-10-15 14:26:51.68CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model
title Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model
spellingShingle Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model
Geninatti Crich, Simonetta
hepatocarcinoma
raton transgenico
MRI
apoferritina
title_short Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model
title_full Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model
title_fullStr Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model
title_full_unstemmed Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model
title_sort Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model
dc.creator.none.fl_str_mv Geninatti Crich, Simonetta
Cutrin, Juan Carlos
Lanzardo, Stefania
Conti, Laura
Kálmán, Ferenc K.
Szabó, Ibolya
Lago, Néstor Rubén
Iolascon, Achille
Aime, Silvio
author Geninatti Crich, Simonetta
author_facet Geninatti Crich, Simonetta
Cutrin, Juan Carlos
Lanzardo, Stefania
Conti, Laura
Kálmán, Ferenc K.
Szabó, Ibolya
Lago, Néstor Rubén
Iolascon, Achille
Aime, Silvio
author_role author
author2 Cutrin, Juan Carlos
Lanzardo, Stefania
Conti, Laura
Kálmán, Ferenc K.
Szabó, Ibolya
Lago, Néstor Rubén
Iolascon, Achille
Aime, Silvio
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv hepatocarcinoma
raton transgenico
MRI
apoferritina
topic hepatocarcinoma
raton transgenico
MRI
apoferritina
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mn-Apo is a highly sensitive MRI contrast agent consisting of ca. 1000 manganese atoms entrapped in the inner cavity of apoferritin. Part of the metallic payload is in the form of Mn2+ ions that endow the nano-sized system with a very high relaxivity that can be exploited to detect hepatocellular carcinoma in mice. Cellular studies showed that Mn-Apo is readily taken up by normal hepatocytes via the ferritin transporting route. Conversely, hepatoma cells (HTC) displayed a markedly reduced ability to entrap Mn-Apo from the culture medium. The i.v. administration of Mn-Apo into C57BL/6 J mice resulted in a marked liver tissue hyperintensity in T1-weighted MR image 20 min after injection. When injected into HBV-tg transgenic mice that spontaneously develop hepatocellular carcinoma (HCC), Mn-Apo allowed a clear delineation of healthy liver tissue and tumor lesions as hyperintense and hypointense T1-weighted MR images, respectively. Immunohistochemistry analysis correlated Mn-Apo cellular uptake to SCARA5 receptor expression. When the MRI contrast induced by Mn-Apo was compared with that induced by Gd–BOPTA (a commercial contrast agent known to enter mouse hepatocytes through organic anion transporters) it was found that only some of the lesions were detected by both agents while others could only be visualized by one of the two. These results suggest that Mn-Apo may be useful to detect otherwise invisible lesions and that the extent of its uptake directly reports the expression/regulation of SCARA5 receptors. Mn-Apo contrastenhanced MR images may therefore contribute to improving HCC lesion detection and characterization.
Fil: Geninatti Crich, Simonetta. University of Turin; Italia
Fil: Cutrin, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Lanzardo, Stefania. University of Turin; Italia
Fil: Conti, Laura. University of Turin; Italia
Fil: Kálmán, Ferenc K.. University of Turin; Italia
Fil: Szabó, Ibolya. University of Turin; Italia
Fil: Lago, Néstor Rubén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentina
Fil: Iolascon, Achille. University of Naples; Italia
Fil: Aime, Silvio. University of Turin; Italia
description Mn-Apo is a highly sensitive MRI contrast agent consisting of ca. 1000 manganese atoms entrapped in the inner cavity of apoferritin. Part of the metallic payload is in the form of Mn2+ ions that endow the nano-sized system with a very high relaxivity that can be exploited to detect hepatocellular carcinoma in mice. Cellular studies showed that Mn-Apo is readily taken up by normal hepatocytes via the ferritin transporting route. Conversely, hepatoma cells (HTC) displayed a markedly reduced ability to entrap Mn-Apo from the culture medium. The i.v. administration of Mn-Apo into C57BL/6 J mice resulted in a marked liver tissue hyperintensity in T1-weighted MR image 20 min after injection. When injected into HBV-tg transgenic mice that spontaneously develop hepatocellular carcinoma (HCC), Mn-Apo allowed a clear delineation of healthy liver tissue and tumor lesions as hyperintense and hypointense T1-weighted MR images, respectively. Immunohistochemistry analysis correlated Mn-Apo cellular uptake to SCARA5 receptor expression. When the MRI contrast induced by Mn-Apo was compared with that induced by Gd–BOPTA (a commercial contrast agent known to enter mouse hepatocytes through organic anion transporters) it was found that only some of the lesions were detected by both agents while others could only be visualized by one of the two. These results suggest that Mn-Apo may be useful to detect otherwise invisible lesions and that the extent of its uptake directly reports the expression/regulation of SCARA5 receptors. Mn-Apo contrastenhanced MR images may therefore contribute to improving HCC lesion detection and characterization.
publishDate 2012
dc.date.none.fl_str_mv 2012-04
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/11336/273058
Geninatti Crich, Simonetta; Cutrin, Juan Carlos; Lanzardo, Stefania; Conti, Laura; Kálmán, Ferenc K.; et al.; Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model; John Wiley & Sons Ltd; Contrast Media & Molecular Imaging; 7; 3; 4-2012; 281-288
1555-4309
CONICET Digital
CONICET
url http://hdl.handle.net/11336/273058
identifier_str_mv Geninatti Crich, Simonetta; Cutrin, Juan Carlos; Lanzardo, Stefania; Conti, Laura; Kálmán, Ferenc K.; et al.; Mn‐loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model; John Wiley & Sons Ltd; Contrast Media & Molecular Imaging; 7; 3; 4-2012; 281-288
1555-4309
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmmi.492
info:eu-repo/semantics/altIdentifier/doi/10.1002/cmmi.492
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons Ltd
publisher.none.fl_str_mv John Wiley & Sons Ltd
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
_version_ 1846082718565138432
score 13.221938

Publicaciones similares