In vivo magnetic resonance imaging of the estrogen receptor in an orthotopic model of human breast cancer
Menée sur un modèle murin de cancer du sein, cette étude évalue la faisabilité d'une technique d'imagerie par résonance magnétique pour l'identification non invasive de tumeurs ER+
Histological overexpression of the estrogen receptor α (ER) is a well established prognostic marker in breast cancer. Non-invasive imaging techniques that could detect ER overexpression would be useful in a variety of settings where patient's biopsies are problematic to obtain. This study focused on developing by in vivo magnetic resonance imaging (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 negative tumors in the model. Lastly, 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.
Cancer Research , résumé, 2011