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Old 03-26-2011, 12:11 PM   #1
Lani
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Join Date: Mar 2006
Posts: 4,778
New protein-based her2-targeted MRI contrast agent to monitor tumors, response to

treatment and noninvasively determine her2 status of tumor/mets

the molecule may be a bit too large to cross the blood-brain barrier (author explained they have not checked); they are looking for commercial partner to make this available, but may have trouble as it is gadolinium- based and may therefore be associated with NSF--a problem usually in those with decreased kidney function where they develop fibrosis(scarring) around joints and organs after receiving gadolinium-based contrast agents for MRI




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

References
Jingjuan Qiao1, Shunyi Li1, Lixia Wei2, Jie Jiang1, Robert Long3, Hui Mao3, Ling Wei1, Liya Wang3, Hua Yang4, Hans E. Grossniklaus4, Zhi-Ren Liu2*, Jenny J. Yang1*
1 Department of Chemistry, Georgia State University, Atlanta, Georgia, United States of America, 2 Department of Biology, Georgia State University, Atlanta, Georgia, United States of America, 3 Department of Radiology, Emory University, Atlanta, Georgia, United States of America, 4 Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States of America
Abstract Top
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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