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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Bibliographic Details
Published in:PloS one 2011-03, Vol.6 (3), p.e18103
Main Authors: 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
Format: Article
Language:English
Subjects:
Angiogenesis
Animal models
Animals
Antibodies - chemistry
Antibodies - immunology
Antigens
Bioindicators
Biology
Biomarkers
Cancer
Cancer therapies
Care and treatment
Cell Line, Tumor
Cells
Chemistry
Contrast agents
Contrast media
Contrast Media - chemistry
Design
Drug discovery
ErbB-2 protein
Fluorescence
Fluorescent Dyes - chemistry
Fluorescent indicators
Health aspects
Humans
Ionizing radiation
Magnetic resonance
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Medicine
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles
NMR
Nuclear magnetic resonance
Pharmacokinetics
Pharmacology
Polyethylene glycol
Prostate cancer
Proteins
Receptor, ErbB-2 - immunology
Tumors
Xenografts
Xenotransplantation
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0018103