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Cross-Species Physiological Assessment of Brain Estrogen Receptor Expression Using 18F-FES and 18F-4FMFES PET Imaging.
Molecular Imaging and Biology ( IF 3.0 ) Pub Date : 2020-07-22 , DOI: 10.1007/s11307-020-01520-w
Michel Paquette 1, 2 , Serge Phoenix 1, 2 , Éric Lavallée 2 , Jacques A Rousseau 1, 2 , Brigitte Guérin 1, 2 , Éric E Turcotte 1, 2 , Roger Lecomte 1, 2
Affiliation  

Purpose

A retrospective analysis was performed of preclinical and clinical data acquired during the evaluation of the estrogen receptor (ER) PET tracer 4-fluoro-11β-methoxy-16α-[18F]-fluoroestradiol (4FMFES) and its comparison with 16α-[18F]-fluoroestradiol (FES) in mice, rats, and humans with a focus on the brain uptake.

Procedures

Breast cancer tumor-bearing female BALB/c mice from a previous study and female Sprague-Dawley rats (control and ovariectomized) were imaged by 4FMFES or FES-PET imaging. Immediately after, low-dose CT was performed in the same bed position. Semi-quantitative analysis was conducted to extract %ID/g data. Small cohorts of mice and rats were imaged with 4FMFES in an ultra-high-resolution small animal PET scanner prototype (LabPET II). Rat brains were dissected and imaged separately with both PET and autoradiography. In parallel, 31 breast cancer patients were enrolled in a clinical phase II study to compare 4FMFES with FES for oncological assessment. Since the head was included in the field of view, brain uptake of discernable foci was measured and reported as SUVMax.

Results

Regardless of the species studied, 4FMFES and FES uptake were relatively uniform in most regions of the brain, except for bilateral foci at the base of the skull, at the midsection of the brain. Anatomical localization of the PET signal using CT image fusion indicates that the signal origins from the pituitary in all studied species. 4FMFES yielded lower pituitary uptake than FES in patients, but an inverse trend was observed in rodents. 4FMFES pituitary contrast was higher than FES in all assessed groups. High-resolution small animal imaging of the brain of rats and mice revealed a supplemental signal anterior to the pituitary, which is likely to be the medial preoptic area. Dissection data further confirmed those findings and revealed additional signals corresponding to the arcuate and ventromedial nuclei, along with the medial and cortical amygdala.

Conclusion

4FMFES allowed visualization of ER expression in the pituitary in humans and two different rodent species with better contrast than FES. Improvement in clinical spatial resolution might allow visualization and analysis of other ER-rich brain areas in humans. Further work is now possible to link 4FMFES pituitary uptake to cognitive functions.


中文翻译:

使用 18F-FES 和 18F-4FMFES PET 成像对脑雌激素受体表达进行跨物种生理评估。

目的

对评估雌激素受体 (ER) PET 示踪剂 4-氟-11β-甲氧基-16α-[ 18 F] -氟雌二醇(4FMFES) 及其与 16α-[ 18 F]-氟雌二醇 (FES) 在小鼠、大鼠和人类中,重点关注大脑摄取。

程序

来自先前研究的带有乳腺癌肿瘤的雌性 BALB/c 小鼠和雌性 Sprague-Dawley 大鼠(对照和卵巢切除)通过 4FMFES 或 FES-PET 成像进行成像。紧接着,在同一床位进行低剂量CT。进行半定量分析以提取 %ID/g 数据。在超高分辨率小动物 PET 扫描仪原型 (LabPET II) 中,使用 4FMFES 对小批量小鼠和大鼠进行成像。分别用 PET 和放射自显影对大鼠大脑进行解剖和成像。同时,31 名乳腺癌患者参加了一项临床 II 期研究,以比较 4FMFES 与 FES 的肿瘤学评估。由于头部包括在视野中,可辨别病灶的大脑摄取被测量并报告为 SUV Max

结果

不管研究的物种是什么,4FMFES 和 FES 的摄取在大脑的大多数区域都相对均匀,除了在颅底、大脑中部的双侧病灶。使用 CT 图像融合对 PET 信号进行解剖定位表明,所有研究物种的信号均来自垂体。4FMFES 在患者中产生比 FES 更低的垂体摄取,但在啮齿动物中观察到相反的趋势。在所有评估组中,4FMFES 垂体对比度高于 FES。大鼠和小鼠大脑的高分辨率小动物成像揭示了垂体前部的补充信号,这可能是内侧视前区。解剖数​​据进一步证实了这些发现,并揭示了与弓状核和腹内侧核相对应的额外信号,

结论

4FMFES 允许可视化人类和两种不同啮齿动物垂体中的 ER 表达,其对比度比 FES 更好。临床空间分辨率的提高可能允许对人类其他富含 ER 的大脑区域进行可视化和分析。进一步的工作现在可以将 4FMFES 垂体摄取与认知功能联系起来。
更新日期:2020-07-22
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