Leung Kam
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Estrogens and progestins 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 of the female reproductive tract, breast, pituitary, hypothalamus, bone, liver, and other tissues, and also in various tissues in men. Estrogens are lipophilic in that they enter the cell passively by diffusion through the cellular membrane. Estrogens bind to ERs that are present in the cytoplasm and the complexes are transported into 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, which induces progestin receptor 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 breast tumors have a better prognosis than women with ER-negative tumors in terms of responsiveness to anti-estrogen treatment. ER content in breast cancer is assessed with receptor binding assays, which suffer from interassay variability, are limited by intrinsic receptor heterogeneity of the tumor, and do not yield information on the ER density in metastases. 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 was cleared from the blood and was metabolized in 20 min with only 20% of [F]FES intact in a study of 15 breast cancer patients (4). Toremifene (TOR) is a chlorinated analog of tamoxifen (5, 6), which was first approved by the United States Food and Drug Administration in the 1970s for use in breast cancer treatment. TOR is primarily used in the treatment of patients with metastatic breast cancer (7). Yurt et al. (8) coupled diethylenetriamine pentaacetic acid (DTPA) to TOR to form (3Z)-4-{4-[2-(dimethylamino)ethoxy]phenyl}-3,4-diphenylbut-3-en-1-yl,-bis[2-(2,6-dioxomorpholin-4-yl)ethyl]glycinate (DTPA-TOR) and radiolabeled the DTPA-TOR with Tc. Tc-DTPA-TOR exhibited high breast tissue/background ratio in female rats.
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、肝脏和其他组织细胞的细胞质和细胞核中，在男性的各种组织中也有发现。雌激素具有亲脂性，它们通过细胞膜扩散被动进入细胞。雌激素与细胞质中存在的雌激素受体结合，复合物被转运到细胞核中。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%将死于转移性乳腺癌。乳腺上皮细胞的生长依赖于雌激素刺激，雌激素刺激可诱导孕激素受体表达。三分之二的乳腺癌表达雌激素受体。肿瘤的雌激素受体状态也是乳腺癌的一个重要预后指标(2)。雌激素受体阳性的乳腺癌女性患者在对抗雌激素治疗的反应方面比雌激素受体阴性的患者预后更好。乳腺癌中的雌激素受体含量通过受体结合试验评估，该试验存在批间差异，受肿瘤内在受体异质性的限制，并且无法提供转移灶中雌激素受体密度的信息。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雌激素受体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被代谢，只有20%的[F]FES保持完整(4)。托瑞米芬(TOR)是他莫昔芬的氯化类似物(5,6)，于20世纪70年代首次被美国食品药品监督管理局批准用于乳腺癌治疗。TOR主要用于治疗转移性乳腺癌患者(7)。于尔特等人(8)将二乙烯三胺五乙酸(DTPA)与TOR偶联形成(3Z)-4-{4-[2-(二甲基氨基)乙氧基]苯基}-3,4-二苯基丁-3-烯-1-基,-双[2-(2,6-二氧代吗啉-4-基)乙基]甘氨酸酯(DTPA-TOR)，并用锝对DTPA-TOR进行放射性标记。锝标记的DTPA-TOR在雌性大鼠中表现出高乳腺组织/本底比值。
