Yang D J, Li C, Kuang L R, Price J E, Buzdar A U, Tansey W, Cherif A, Gretzer M, Kim E E, Wallace S
Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Life Sci. 1994;55(1):53-67. doi: 10.1016/0024-3205(94)90081-7.
Tamoxifen binds to estrogen receptors (ERs) and prevents breast cancer cell proliferation. This study is aimed at developing a ligand for imaging ER (+) breast tumors by positron emission tomography (PET) or single photon emission computed tomography (SPECT). [18F]-Labeled tamoxifen analogue ([18F]FTX) was prepared in 30-40% yield and [131I]-labeled tamoxifen analogue ([131I]ITX) was prepared in 20-25% yield. In mammary tumor-bearing rats, the biodistribution of [18F]FTX at 2 h showed a tumor uptake value (% injected dose/gram tissue) of 0.41 +/- 0.07; when rats were pretreated with diethylstilbestrol (DES), the value changed to 0.24 +/- 0.017. [131I]ITX at 6 h showed a tumor uptake value of 0.26 +/- 0.166; when rats were pretreated with DES, the value changed to 0.22 +/- 0.044. Priming tumor-bearing rats with estradiol, a tumor uptake value for [131I]ITX was increased to 0.48 +/- 0.107 at 6 h. In the [3H]estradiol receptor assay, tumors had a mean estrogen receptor density of 7.5 fmol/mg of protein. In gamma scintigraphic imaging studies with [131I]ITX, the rabbit uterus uptake can be blocked by pretreatment with DES. Both iodo-tamoxifen and tamoxifen reduced ER(+) breast tumor growth at the dose of 50 micrograms in tumor-bearing mice. The findings indicate that tamoxifen analogue uptake in tumors occurs via an ER-mediated process. Both analogues should have potential for diagnosing functioning ER(+) breast cancer.
他莫昔芬与雌激素受体（ERs）结合，可阻止乳腺癌细胞增殖。本研究旨在开发一种用于通过正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）对ER（+）乳腺肿瘤进行成像的配体。以30 - 40%的产率制备了[18F]标记的他莫昔芬类似物（[18F]FTX），以20 - 25%的产率制备了[131I]标记的他莫昔芬类似物（[131I]ITX）。在荷乳腺肿瘤的大鼠中，[18F]FTX在2小时时的生物分布显示肿瘤摄取值（%注射剂量/克组织）为0.41±0.07；当大鼠用己烯雌酚（DES）预处理时，该值变为0.24±0.017。[131I]ITX在6小时时显示肿瘤摄取值为0.26±0.166；当大鼠用DES预处理时，该值变为0.22±0.044。用雌二醇对荷肿瘤大鼠进行预处理后，[131I]ITX在6小时时的肿瘤摄取值增加到0.48±0.107。在[3H]雌二醇受体测定中，肿瘤的平均雌激素受体密度为7.5 fmol/毫克蛋白质。在用[131I]ITX进行的γ闪烁成像研究中，兔子宫摄取可被DES预处理阻断。在荷肿瘤小鼠中，碘他莫昔芬和他莫昔芬在50微克剂量时均能降低ER（+）乳腺肿瘤的生长。这些发现表明肿瘤中他莫昔芬类似物的摄取是通过ER介导的过程发生的。这两种类似物都具有诊断功能性ER（+）乳腺癌的潜力。
