A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors

Abstract C-X-C chemokine receptor 4 (CXCR4) is over-expressed in multiple human cancers and correlates with tumor aggressiveness, poor prognosis and increased risk for distant metastases. Imaging agents for CXCR4 are thus highly desirable. We developed a novel CXCR4-targeted near-infrared (NIR) fluo...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Sara Santagata, Luigi Portella, Maria Napolitano, Adelaide Greco, Crescenzo D’Alterio, Maria Vittoria Barone, Antonio Luciano, Matteo Gramanzini, Luigi Auletta, Claudio Arra, Antonella Zannetti, Stefania Scala
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/2e67fe00267c494d87da49165cfcd85e
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:2e67fe00267c494d87da49165cfcd85e
record_format dspace
spelling oai:doaj.org-article:2e67fe00267c494d87da49165cfcd85e2021-12-02T11:52:16ZA novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors10.1038/s41598-017-02818-62045-2322https://doaj.org/article/2e67fe00267c494d87da49165cfcd85e2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02818-6https://doaj.org/toc/2045-2322Abstract C-X-C chemokine receptor 4 (CXCR4) is over-expressed in multiple human cancers and correlates with tumor aggressiveness, poor prognosis and increased risk for distant metastases. Imaging agents for CXCR4 are thus highly desirable. We developed a novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) conjugating the new developed CXCR4 peptidic antagonist Peptide R with the NIR fluorescent dye VivoTag-S750. Specific CXCR4 binding was obtained in cells overexpressing human CXCR4 (B16-hCXCR4 and human melanoma cells PES43), but not in CXCR4 low expressing cells (FB-1). Ex vivo evaluation demonstrated that PepR-NIR750 specifically detects B16-hCXCR4-derived subcutaneous tumors and lung metastases. Fluorescence Molecular Tomography (FMT) in vivo imaging was performed on mice carrying subcutaneous CHO and CHO-CXCR4 tumors. PepR-NIR750 accumulates only in CXCR4-positive expressing subcutaneous tumors. Additionally, an intense NIR fluorescence signal was detected in PES43-derived lung metastases of nude mice injected with PepR-NIR750 versus mice injected with VivoTag-S750. With a therapeutic intent, mice bearing PES43-derived lung metastases were treated with Peptide R. A the dramatic reduction in PES43-derived lung metastases was detected through a decrease of the PepR-NIR750 signal. PepR-NIR750 is a specific probe for non-invasive detection of human high CXCR4-expressing tumors and metastatic lesion and thus a valuable tool for cancer molecular imaging.Sara SantagataLuigi PortellaMaria NapolitanoAdelaide GrecoCrescenzo D’AlterioMaria Vittoria BaroneAntonio LucianoMatteo GramanziniLuigi AulettaClaudio ArraAntonella ZannettiStefania ScalaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sara Santagata
Luigi Portella
Maria Napolitano
Adelaide Greco
Crescenzo D’Alterio
Maria Vittoria Barone
Antonio Luciano
Matteo Gramanzini
Luigi Auletta
Claudio Arra
Antonella Zannetti
Stefania Scala
A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors
description Abstract C-X-C chemokine receptor 4 (CXCR4) is over-expressed in multiple human cancers and correlates with tumor aggressiveness, poor prognosis and increased risk for distant metastases. Imaging agents for CXCR4 are thus highly desirable. We developed a novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) conjugating the new developed CXCR4 peptidic antagonist Peptide R with the NIR fluorescent dye VivoTag-S750. Specific CXCR4 binding was obtained in cells overexpressing human CXCR4 (B16-hCXCR4 and human melanoma cells PES43), but not in CXCR4 low expressing cells (FB-1). Ex vivo evaluation demonstrated that PepR-NIR750 specifically detects B16-hCXCR4-derived subcutaneous tumors and lung metastases. Fluorescence Molecular Tomography (FMT) in vivo imaging was performed on mice carrying subcutaneous CHO and CHO-CXCR4 tumors. PepR-NIR750 accumulates only in CXCR4-positive expressing subcutaneous tumors. Additionally, an intense NIR fluorescence signal was detected in PES43-derived lung metastases of nude mice injected with PepR-NIR750 versus mice injected with VivoTag-S750. With a therapeutic intent, mice bearing PES43-derived lung metastases were treated with Peptide R. A the dramatic reduction in PES43-derived lung metastases was detected through a decrease of the PepR-NIR750 signal. PepR-NIR750 is a specific probe for non-invasive detection of human high CXCR4-expressing tumors and metastatic lesion and thus a valuable tool for cancer molecular imaging.
format article
author Sara Santagata
Luigi Portella
Maria Napolitano
Adelaide Greco
Crescenzo D’Alterio
Maria Vittoria Barone
Antonio Luciano
Matteo Gramanzini
Luigi Auletta
Claudio Arra
Antonella Zannetti
Stefania Scala
author_facet Sara Santagata
Luigi Portella
Maria Napolitano
Adelaide Greco
Crescenzo D’Alterio
Maria Vittoria Barone
Antonio Luciano
Matteo Gramanzini
Luigi Auletta
Claudio Arra
Antonella Zannetti
Stefania Scala
author_sort Sara Santagata
title A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors
title_short A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors
title_full A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors
title_fullStr A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors
title_full_unstemmed A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors
title_sort novel cxcr4-targeted near-infrared (nir) fluorescent probe (peptide r-nir750) specifically detects cxcr4 expressing tumors
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/2e67fe00267c494d87da49165cfcd85e
work_keys_str_mv AT sarasantagata anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT luigiportella anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT marianapolitano anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT adelaidegreco anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT crescenzodalterio anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT mariavittoriabarone anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT antonioluciano anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT matteogramanzini anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT luigiauletta anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT claudioarra anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT antonellazannetti anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT stefaniascala anovelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT sarasantagata novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT luigiportella novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT marianapolitano novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT adelaidegreco novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT crescenzodalterio novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT mariavittoriabarone novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT antonioluciano novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT matteogramanzini novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT luigiauletta novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT claudioarra novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT antonellazannetti novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
AT stefaniascala novelcxcr4targetednearinfrarednirfluorescentprobepeptidernir750specificallydetectscxcr4expressingtumors
_version_ 1718395093441839104