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lüll Gadolinium-Hexyl-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid-progesterone Leung KMolecular Imaging and Contrast Agent Database (MICAD)-/-ä 2004[]; ä (ä): äEstrogens and progesterones are endogenous hormones that produce many physiological effects (1). Estrogens act primarily by regulating gene expression. Estrogen receptors (ERs) are found in the cytoplasm and nucleus of cells in the female reproductive tract, breast, pituitary gland, hypothalamus, bone, liver, and other tissues, as well as in various tissues in men. Estrogens are lipophilic in that they enter the cell passively by diffusion through the cellular membrane. They bind to ERs in the cytoplasm and are transported to the nucleus. Breast cancer is the most common malignancy in women. Approximately 33% of women who have this disease will die of disseminated breast cancer. The growth of breast epithelial cells is dependent on estrogen stimulation to induce progesterone receptor (PR) expression. Two-thirds of breast carcinomas express ERs. It has also been established that the ER status of the tumor is an important prognostic indicator in breast cancer (2). Women with ER-positive and PR-positive breast tumors have a better prognosis than women with ER-negative and PR-negative tumors in terms of responsiveness to anti-estrogen treatment. ER content in breast cancer has been assessed in vitro with receptor binding assays, which suffer from inter-assay variability and are also limited by intrinsic receptor heterogeneity of the primary and metastatic tumors. 16alpha-[(18)F]Fluoro-17beta-estradiol ([(18)F]FES) has been proven to be a valuable tracer for studies of the ER status of primary and metastatic breast cancer (3). However, [(18)F]FES is cleared from the blood and metabolized in 20 min with only 20% of [(18)F]FES intact in a study with 15 breast cancer patients (4). Similarly, a [(18)F]-labeled progestin is also metabolized rapidly in humans (5). For magnetic resonance imaging (MRI), Sukerkar et al. (6) found that coupling of gadolinium-hexyl-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (Gd-hexyl-DO3A) to the C21 hydroxyl group of 21-hydroxylprogesterone renders the MRI probe (ProGlo) inaccessible for metabolism but still able to bind specifically to PR(+) breast cancer cells. ProGlo was shown to accumulate in PR-rich uterus and PR(+) tumors in vivo in mice.ä |