Moon Byung Seok, Carlson Kathryn E, Katzenellenbogen John A, Choi Tae Hyun, Chi Dae Yoon, Kim Jung Young, Cheon Gi Jeong, Koh Hun Yeong, Lee Kyo Chul, An Gwangil
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Bioorg Med Chem. 2009 May 1;17(9):3479-88. doi: 10.1016/j.bmc.2009.02.064. Epub 2009 Mar 9.
We have investigated halogen-substituted non-steroidal estrogens with selective binding affinity for the estrogen receptor beta (ERbeta that might be used for imaging the levels of this ER-subtype in breast tumors by positron emission tomography (PET). Based on diarylpropionitrile (DPN, 1a), a compound previously reported that has a 72-fold binding selectivity for ERbeta, we developed a series of DPN analogs having methyl-, hydroxyl-, and halogen substituents, including fluoroethyl and fluoropropyl groups. In competitive radiometric binding assays with [(3)H]estradiol, all of these DPN analogs showed high ERbeta/ERalpha selectivity; while the selectivity varied, in some cases it reached nearly 300-fold (RBA: ERalpha, 0.023%; ERbeta, 6.25%). The absolute ERbeta binding affinities, however, were not sufficient to merit further consideration for developing these ligands as PET imaging agents.
我们研究了对雌激素受体β（ERβ）具有选择性结合亲和力的卤素取代非甾体雌激素，这类雌激素或许可用于通过正电子发射断层扫描（PET）对乳腺肿瘤中该ER亚型的水平进行成像。基于二芳基丙腈（DPN，1a）——一种先前报道的对ERβ具有72倍结合选择性的化合物，我们开发了一系列具有甲基、羟基和卤素取代基（包括氟乙基和氟丙基）的DPN类似物。在与[³H]雌二醇的竞争性放射性结合试验中，所有这些DPN类似物均表现出高ERβ/ERα选择性；虽然选择性有所不同，但在某些情况下接近300倍（相对结合亲和力：ERα，0.023%；ERβ，6.25%）。然而，这些配体的绝对ERβ结合亲和力不足以使其作为PET成像剂得到进一步考虑。
