Synthesis and biological evaluation of two agents for imaging estrogen receptor β by positron emission tomography: challenges in PET imaging of a low abundance target.
Synthesis and biological evaluation of two agents for imaging estrogen receptor β by positron emission tomography: challenges in PET imaging of a low abundance target.
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DOI：
10.1016/j.nucmedbio.2012.05.011
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发表时间：
2012-11
影响因子：
3.1
通讯作者：
Katzenellenbogen JA
中科院分区：
文献类型：
--
作者：
Lee JH;Peters O;Lehmann L;Dence CS;Sharp TL;Carlson KE;Zhou D;Jeyakumar M;Welch MJ;Katzenellenbogen JA
独立测量乳腺癌中雌激素受体ERα和ERβ的水平可以改善内分泌治疗的获益预测。虽然ERα水平可以通过使用16α-[18 F]氟雌二醇（FES）的正电子发射断层扫描（PET）测量，但尚未报道通过PET成像ERβ的有效药物。我们已经制备了氟-18标记形式的8β-（2-氟乙基）雌二醇（8BFEE 2），这是一种ERβ选择性甾体雌激素8β-乙烯基雌二醇的类似物;实现了氟-18的有效掺入，但需要非常剧烈的条件。我们已经检查了该化合物以及Br-041的生物分布，Br-041是一种已知的非甾体ERβ选择性配体（ERB-041）的类似物，用溴-76标记。在未成熟的雌性啮齿动物中进行了研究，采用各种药理学和内分泌干扰来评估ERβ的摄取选择性。[18 F] 8BFEE 2或[76 Br]Br-041均未发现ERβ介导的摄取。增加靶组织ERβ含量的尝试无效，未能改善生物分布选择性。由于在绝对水平上，ERβ水平在所有靶组织中均较低，因此这些研究强调需要开发改进的体内模型，以评价用于PET成像的ERβ选择性放射性药物。正在开发的基因工程乳腺癌细胞以调控的方式表达ERα或ERβ，在免疫受损小鼠中作为异种移植物生长，可以证明对未来开发ER亚型选择性放射性药物的研究有用。
Independent measurement of the levels of both the estrogen receptors, ERα and ERβ, in breast cancer could improve prediction of benefit from endocrine therapies. While ERα levels can be measured by positron emission tomography (PET) using 16α-[18F]fluoroestradiol (FES), no effective agent for imaging ERβ by PET has yet been reported. We have prepared the fluorine-18 labeled form of 8β-(2-fluoroethyl)estradiol(8BFEE2), an analog of an ERβ-selective steroidal estrogen, 8β-vinylestradiol; efficient incorporation of fluorine-18 was achieved, but required very vigorous conditions. We have examined the biodistribution of this compound, as well as ofBr-041, an analog of a known non-steroidal ERβ-selective ligand (ERB-041), labeled with bromine-76. Studies were done in immature female rodents, with various pharmacological and endocrine perturbations to assess ERβ selectivity of uptake. Little evidence of ERβ-mediated uptake was observedwith either [18F]8BFEE2 or [76Br]Br-041. Attempts to increase the ERβ content of target tissues were not effective and failed to improve biodistribution selectivity. Because on an absolute level, ERβ levels are low in all target tissues, these studies have highlighted the need to develop improved in vivo models for evaluating ERβ-selective radiopharmaceuticals for use in PET imaging. Genetically engineered breast cancer cells that are being developed to express either ERα or ERβ in a regulated manner, grown as xenografts in immune-compromised mice, could prove useful for future studies to develop ER subtype-selective radiopharmaceuticals.
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影响因子：
9.7
作者：
Girault, I;Andrieu, C;Lidereau, R
通讯作者：
Lidereau, R
影响因子：
7.3
作者：
Compton, DR;Sheng, SB;Katzenellenbogen, JA
通讯作者：
Katzenellenbogen, JA
影响因子：
4.8
作者：
Chang, Edmund C.;Frasor, Jonna;Katzenellenbogen, Benita S.
通讯作者：
Katzenellenbogen, Benita S.
影响因子：
11.5
作者：
Esslimani-Sahla, M;Kramar, A;Rochefort, H
通讯作者：
Rochefort, H
DOI：
10.1073/pnas.0306720101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Hegele-Hartung, C;Siebel, P;Fritzemeier, KH
通讯作者：
Fritzemeier, KH