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HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent

The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomark...

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Autores principales: Qiao, Jingjuan, Li, Shunyi, Wei, Lixia, Jiang, Jie, Long, Robert, Mao, Hui, Wei, Ling, Wang, Liya, Yang, Hua, Grossniklaus, Hans E., Liu, Zhi-Ren, Yang, Jenny J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063795/
https://www.ncbi.nlm.nih.gov/pubmed/21455310
http://dx.doi.org/10.1371/journal.pone.0018103
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author Qiao, Jingjuan
Li, Shunyi
Wei, Lixia
Jiang, Jie
Long, Robert
Mao, Hui
Wei, Ling
Wang, Liya
Yang, Hua
Grossniklaus, Hans E.
Liu, Zhi-Ren
Yang, Jenny J.
author_facet Qiao, Jingjuan
Li, Shunyi
Wei, Lixia
Jiang, Jie
Long, Robert
Mao, Hui
Wei, Ling
Wang, Liya
Yang, Hua
Grossniklaus, Hans E.
Liu, Zhi-Ren
Yang, Jenny J.
author_sort Qiao, Jingjuan
collection PubMed
description The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti-cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice models. In addition to its 100-fold higher dose efficiency compared to clinically approved non-targeting contrast agent DTPA, our developed agent also exhibits advantages in crossing the endothelial boundary, tissue distribution, and tumor tissue retention over reported contrast agents as demonstrated by even distribution of the imaging probe across the entire tumor mass. This contrast agent will provide a powerful tool for quantitative assessment of molecular markers, and improved resolution for diagnosis, prognosis and drug discovery.
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spelling pubmed-30637952011-03-31 HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent Qiao, Jingjuan Li, Shunyi Wei, Lixia Jiang, Jie Long, Robert Mao, Hui Wei, Ling Wang, Liya Yang, Hua Grossniklaus, Hans E. Liu, Zhi-Ren Yang, Jenny J. PLoS One Research Article The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti-cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice models. In addition to its 100-fold higher dose efficiency compared to clinically approved non-targeting contrast agent DTPA, our developed agent also exhibits advantages in crossing the endothelial boundary, tissue distribution, and tumor tissue retention over reported contrast agents as demonstrated by even distribution of the imaging probe across the entire tumor mass. This contrast agent will provide a powerful tool for quantitative assessment of molecular markers, and improved resolution for diagnosis, prognosis and drug discovery. Public Library of Science 2011-03-24 /pmc/articles/PMC3063795/ /pubmed/21455310 http://dx.doi.org/10.1371/journal.pone.0018103 Text en Qiao et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Qiao, Jingjuan
Li, Shunyi
Wei, Lixia
Jiang, Jie
Long, Robert
Mao, Hui
Wei, Ling
Wang, Liya
Yang, Hua
Grossniklaus, Hans E.
Liu, Zhi-Ren
Yang, Jenny J.
HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent
title HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent
title_full HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent
title_fullStr HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent
title_full_unstemmed HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent
title_short HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent
title_sort her2 targeted molecular mr imaging using a de novo designed protein contrast agent
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063795/
https://www.ncbi.nlm.nih.gov/pubmed/21455310
http://dx.doi.org/10.1371/journal.pone.0018103
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