title: In vivo magnetic resonance imaging of the estrogen receptor in an orthotopic model of human breast cancer.
abstract: Histologic overexpression of the estrogen receptor α (ER) is a well-established prognostic marker in breast cancer. Noninvasive imaging techniques that could detect ER overexpression would be useful in a variety of settings where patients' biopsies are problematic to obtain. This study focused on developing, by in vivo MRI, strategies to measure the level of ER expression in an orthotopic mouse model of human breast cancer. Specifically, novel ER-targeted contrast agents based on pyridine-tetra-acetate-Gd(III) chelate (PTA-Gd) conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd) were examined in ER-positive or ER-negative tumors. Detection of specific interactions of EPTA-Gd with ER were documented that could differentiate ER-positive and ER-negative tumors. In vivo competition experiments confirmed that the enhanced detection capability of EPTA-Gd was based specifically on ER targeting. In contrast, PTA-Gd acted as an extracellular probe that enhanced ER detection similarly in either tumor type, confirming a similar vascular perfusion efficiency in ER-positive and ER-negative tumors in the model. Finally, TPTA-Gd accumulated selectively in muscle and could not preferentially identify ER-positive tumors. Together, these results define a novel MRI probe that can permit selective noninvasive imaging of ER-positive tumors in vivo.
authors: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors: Adi
authors: A
authors: Pais
authors: Chidambaram
authors: C
authors: Gunanathan
authors: Raanan
authors: R
authors: Margalit
authors: Inbal Eti
authors: IE
authors: Biton
authors: Ady
authors: A
authors: Yosepovich
authors: David
authors: D
authors: Milstein
authors: Hadassa
authors: H
authors: Degani
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005682:Gadolinium / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009942:Organometallic Compounds / Q000737:chemistry; D015203:Reproducibility of Results; D013629:Tamoxifen / Q000737:chemistry / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000085:Acetates; D003287:Contrast Media; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D009942:Organometallic Compounds; D013629:Tamoxifen; D004958:Estradiol; D005682:Gadolinium