title: HER2 targeted molecular MR imaging using a de novo designed protein contrast agent.
abstract: 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.
authors: Department of Chemistry, Georgia State University, Atlanta, Georgia, United States of America.
authors: Jingjuan
authors: J
authors: Qiao
authors: Shunyi
authors: S
authors: Li
authors: Lixia
authors: L
authors: Wei
authors: Jie
authors: J
authors: Jiang
authors: Robert
authors: R
authors: Long
authors: Hui
authors: H
authors: Mao
authors: Ling
authors: L
authors: Wei
authors: Liya
authors: L
authors: Wang
authors: Hua
authors: H
authors: Yang
authors: Hans E
authors: HE
authors: Grossniklaus
authors: Zhi-Ren
authors: ZR
authors: Liu
authors: Jenny J
authors: JJ
authors: Yang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
chemical_list: D000906:Antibodies; D003287:Contrast Media; D005456:Fluorescent Dyes; D018719:Erb-b2 Receptor Tyrosine Kinases