大鼠脑内雌激素受体的活体成像：16α-18F-氟-17β-雌二醇 PET 研究。

In vivo imaging of brain estrogen receptors in rats: a 16α-18F-fluoro-17β-estradiol PET study.

机构信息

Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

出版信息

J Nucl Med. 2014 Mar;55(3):481-7. doi: 10.2967/jnumed.113.128751. Epub 2014 Jan 30.

DOI:10.2967/jnumed.113.128751

PMID:24481026

Abstract

UNLABELLED

The steroid hormone estrogen is important for brain functioning and is thought to be involved in brain diseases, such as Alzheimer disease and depression. The action of estrogen is mediated by estrogen receptors (ERs). To understand the role of estrogens in brain functioning, it is important to study ERs in the brain. The aims of the present study were to determine whether ERs could be measured in the rat brain by PET with the ER ligand 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) and to evaluate whether tracer uptake was affected by endogenous estrogen.

METHODS

Small-animal PET was used to determine (18)F-FES uptake in female rats in the diestrous phase of the estrous cycle, the proestrous phase, and after ovariectomy. Coinjection of (18)F-FES with 17β-estradiol was performed to determine whether tracer binding was specific for ERs. Additionally, (18)F-FES uptake was quantified with kinetic modeling in female rats in the proestrous phase and after ovariectomy and in male rats.

RESULTS

The highest levels of uptake of (18)F-FES were found (in descending order) in the pituitary, hypothalamus, bed nucleus of the stria terminalis, and amygdala. Other brain regions showed low levels of brain uptake. The level of (18)F-FES uptake was higher in the pituitary and hypothalamus in rats after ovariectomy than in rats in the proestrous phase. Coinjection with 17β-estradiol resulted in a decrease in (18)F-FES uptake in the pituitary and hypothalamus. The volume of distribution and binding potential determined with kinetic modeling were higher in the pituitary than in the other brain regions in all 3 groups. No differences were found among the groups.

CONCLUSION

(18)F-FES PET imaging of ER availability in the rat brain is feasible for brain regions with high ER densities.

摘要

未加说明

类固醇激素雌激素对大脑功能很重要，被认为与阿尔茨海默病和抑郁症等脑部疾病有关。雌激素的作用是通过雌激素受体（ERs）介导的。为了了解雌激素在大脑功能中的作用，研究大脑中的 ERs 非常重要。本研究的目的是确定是否可以通过正电子发射断层扫描（PET）用雌激素受体配体 16α-（18）F-氟-17β-雌二醇（（18）F-FES）测量大鼠大脑中的 ERs，并评估内源性雌激素是否会影响示踪剂摄取。

方法

使用小动物 PET 来确定在发情周期的间情期、发情前期和卵巢切除后的雌性大鼠中（18）F-FES 的摄取。（18）F-FES 与 17β-雌二醇共注射以确定示踪剂结合是否特异性针对 ERs。此外，在发情前期和卵巢切除后的雌性大鼠以及雄性大鼠中，通过动力学建模来定量（18）F-FES 的摄取。

结果

（18）F-FES 的摄取量最高（按降序排列）分别位于垂体、下丘脑、终纹床核和杏仁核。其他脑区的脑摄取水平较低。卵巢切除后的大鼠的垂体和下丘脑的（18）F-FES 摄取量高于发情前期的大鼠。共注射 17β-雌二醇会导致垂体和下丘脑的（18）F-FES 摄取量减少。用动力学建模确定的分布容积和结合势在所有 3 组中均高于其他脑区。各组之间没有差异。