Leung Kam
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Estrogens 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 with receptor binding assays, which suffer from inter-assay variability and are also limited by intrinsic receptor heterogeneity of the primary and metastatic tumors. 16α-[F]Fluoro-17β-estradiol ([F]FES) has been proven to be a valuable tracer for studies of the ER status of primary and metastatic breast cancer (3). However, [F]FES is cleared from the blood and metabolized in 20 min with only 20% of [F]FES intact in a study with 15 breast cancer patients (4). Similarly, a [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 mice.
雌激素和孕激素是产生多种生理效应的内源性激素（1）。雌激素主要通过调节基因表达发挥作用。雌激素受体（ERs）存在于女性生殖道、乳腺、垂体、下丘脑、骨骼、肝脏及其他组织的细胞胞质和细胞核中，在男性的各种组织中也有发现。雌激素具有亲脂性，可通过扩散被动穿过细胞膜进入细胞。它们与胞质中的ERs结合并被转运至细胞核。乳腺癌是女性中最常见的恶性肿瘤。患有这种疾病的女性中约有33%会死于转移性乳腺癌。乳腺上皮细胞的生长依赖于雌激素刺激以诱导孕激素受体（PR）表达。三分之二的乳腺癌表达ERs。肿瘤的ER状态也是乳腺癌的一个重要预后指标，这一点也已得到证实（2）。就对抗雌激素治疗的反应而言，ER阳性和PR阳性乳腺肿瘤的女性比ER阴性和PR阴性肿瘤的女性预后更好。乳腺癌中的ER含量已通过受体结合测定法进行评估，该方法存在测定间变异性，且也受原发性和转移性肿瘤内在受体异质性的限制。16α-[F]氟-17β-雌二醇（[F]FES）已被证明是研究原发性和转移性乳腺癌ER状态的一种有价值的示踪剂（3）。然而，在一项对15名乳腺癌患者的研究中，[F]FES在20分钟内从血液中清除并代谢，只有20%的[F]FES保持完整（4）。同样，一种[F]标记的孕激素在人体内也迅速代谢（5）。对于磁共振成像（MRI），苏克尔卡尔等人（6）发现，将钆-己基-1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸（钆-己基-DO3A）与21-羟基孕酮的C21羟基偶联，使MRI探针（ProGlo）无法代谢，但仍能特异性结合PR（+）乳腺癌细胞。ProGlo在小鼠富含PR的子宫和PR（+）肿瘤中显示出聚集。
