Chelation-Tamoxifen Conjugates for Imaging of Estrogen Receptors

Skye Hsin Hsien Yeh, Wei Chung Chang, Shu Meng Hsu, Ming Hsien Lin, Min Ching Chung, Chi Shiang Ke, Yen Chun Lee, Chorng Jer Hwang, David J. Yang

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)


Background: The differential diagnosis of estrogen receptor-positive (ER+) pathway-activated systems by using a labeled antiestrogen helps to select the patients for optimal response to endocrine therapy and to discontinue the treatment when resistance occurs. The authors' purpose was to synthesize chelator-tamoxifen conjugates for imaging ER (+) diseases. Materials and Methods: A hydroxypropyl linker was incorporated between either cyclam or cyclam diacetic acid and tamoxifen analog to produce SC-05-L-1 (Z-1-(1,4,8,11-tetraazacyclotetradecan-1-yl)-3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)propan-2-ol) and SC-05-N-1 (Z-2,2′-(4-(3-((5-(4-(2-(diethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-yl)oxy)-2-hydroxy-propyl)-1,4,8,11-tetraazacyclotetradecane-1,8-diyl)diacetic acid), respectively. In vitro cell uptake and cell/media ratios of 99mTc-SC-05-L-1 and 99mTc- SC-05-N-1 in ER (+) ovarian cancer cells (TOV-112D and OVCAR3) were performed. To ascertain the specificity of cell uptake, the cell uptake was blocked with estrone. In vivo 99mTc-SC-05-L-1 or 99mTc-SC-05-N-1 single-photon emission computed tomography/computed tomography was conducted in tumor-bearing rodents and compared to 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/magnetic resonance imaging (a reference technology). Results: The radiochemical purities of 99mTc-SC-05-L-1 and 99mTc-SC-05-N-1 were greater than 99% (n = 10). 99mTc-SC-05-L-1 had higher cell/media ratios than 99mTc-SC-05-N-1 in OVCAR-3 ER (+) cells. The cell uptake of 99mTc-SC-05-L-1 was blocked 80% by estrone indicating an ER-mediated process occurred. 99mTc-SC-05-N-1 was further selected for in vivo imaging studies due to higher maximum tolerated dose and superior water solubility than 99mTc-SC-05-L-1. 99mTc-SC-05-N-1 showed higher tumor uptake and tumor/muscle count density ratios than 18F-FDG in tumor-bearing rodents. Conclusion: 99mTc-SC-05-N-1 showed better differential diagnosis of ovarian tumors than 18F-FDG, indicating great promising in chelator-tamoxifen conjugate for ER pathway-directed systems imaging.

頁(從 - 到)30-40
期刊Cancer Biotherapy and Radiopharmaceuticals
出版狀態Published - 2月 2022


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