使用 [F]-DPA-714 对暴露于蓝光的小鼠进行视网膜炎症的 PET 成像。

PET imaging of retinal inflammation in mice exposed to blue light using [F]-DPA-714.

机构信息

Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu Province, China.

NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine. Wuxi, Jiangsu Province, China.

出版信息

Mol Vis. 2022 Dec 31;28:507-515. eCollection 2022.

PMID:37089700

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10115360/

Abstract

PURPOSE

Positron emission tomography (PET) is widely used in high-precision imaging, which may provide a simple and noninvasive method for the detection of pathology and therapeutic effects. [F]-DPA-714 is a second-generation translocator protein (TSPO) positron emission tomography radiotracer that shows great promise in a model of neuroinflammation. In this study, [F]-DPA-714 micro-PET imaging was used to evaluate retinal inflammation in mice exposed to blue light, a well-established model of age-related macular degeneration (AMD) for molecular mechanism research and drug screening.

METHODS

C57BL/6J melanized mice were subjected to 10,000, 15,000, and 20,000 lux blue light for 5 days (8 h/day) to develop the retinal injury model, and the structure and function of the retina were assessed using hematoxylin-eosin (HE) staining, electroretinography (ERG), and terminal-deoxynucleotidyl transferase (TdT)-mediated nick-end labeling (TUNEL) immunostaining. Then, [F]-DPA-714 was injected approximately 100 μCi through each tail vein, and static imaging was performed 1 h after injection. Finally, the mice eyeballs were collected for biodistribution and immune analysis.

RESULTS

The blue light exposure significantly destroyed the structure and function of the retina, and the uptake of [F]-DPA-714 in the retinas of the mice exposed to blue light were the most significantly upregulated, which was consistent with the biodistribution data. In addition, the immunohistochemical, western blot, and immunofluorescence data showed an increase in microglial TSPO expression.

CONCLUSIONS

[F]-DPA-714 micro-PET imaging might be a good method for evaluating early inflammatory status during retinal pathology.

摘要

目的

正电子发射断层扫描（PET）在高精度成像中得到广泛应用，它可能为病理学和治疗效果的检测提供一种简单、无创的方法。[F]-DPA-714 是一种第二代转位蛋白（TSPO）正电子发射断层扫描放射性示踪剂，在神经炎症模型中显示出巨大的应用前景。在这项研究中，[F]-DPA-714 微 PET 成像用于评估暴露于蓝光的小鼠的视网膜炎症，这是一种成熟的年龄相关性黄斑变性（AMD）模型，用于分子机制研究和药物筛选。

方法

C57BL/6J 黑化小鼠暴露于 10000、15000 和 20000 勒克斯蓝光下 5 天（每天 8 小时），以建立视网膜损伤模型，使用苏木精-伊红（HE）染色、视网膜电图（ERG）和末端脱氧核苷酸转移酶（TdT）介导的缺口末端标记（TUNEL）免疫染色评估视网膜的结构和功能。然后，通过每条尾巴静脉注射约 100μCi [F]-DPA-714，注射后 1 小时进行静态成像。最后，收集小鼠眼球进行生物分布和免疫分析。