已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Imaging Pulmonary Fibrosis and Treatment Efficacy In Vivo with Autotaxin-Specific PET Ligand [18F]ATX-1905

自交轴蛋白 吡非尼酮 医学 特发性肺纤维化 纤维化 任天堂 肺纤维化 博莱霉素 病理 炎症 内科学 化疗 溶血磷脂酸 受体
作者
Xiaoyun Deng,Junyi Liu,Jianyuan Zhou,Yifan Shi,Shuang Song,Jiahui Chen,Yinlong Li,Bo Yu,Steven H. Liang,Xiaohua Zhu
出处
期刊:Molecular Pharmaceutics [American Chemical Society]
卷期号:21 (10): 5171-5181 被引量:1
标识
DOI:10.1021/acs.molpharmaceut.4c00571
摘要

Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by unpredictable progression and limited therapeutic options. Current diagnosis relies on high resolution computed tomography (HRCT), which may not adequately capture early signs of deterioration. The enzyme autotaxin (ATX) emerges as a prominently expressed extracellular secretory enzyme in the lungs of IPF patients. The objective of this study was to evaluate the effectiveness of 18F-labeled ATX-targeted tracer [18F]ATX-1905, in comparison with [18F]FDG, for early fibrosis diagnosis, disease evolution monitoring, and treatment efficacy assessment in bleomycin-induced pulmonary fibrosis (BPF) models. To assess treatment efficacy, mice were treated with two commonly used drugs for IPF, pirfenidone or nintedanib, from Day 9 to Day 23 postbleomycin administration. Lung tissue assessments encompassed inflammation severity via H&E staining, and Ashcroft scoring via Masson staining, alongside quantification of ATX expression through ELISA. Positron emission tomography (PET) imaging employing [18F]FDG and [18F]ATX-1905 tracked disease progression pre- and post-treatment. The extent of pulmonary fibrosis corresponded to changes in ATX expression levels in the BPF mouse model. Notably, [18F]ATX-1905 exhibited elevated uptake in BPF lungs during the progression of the disease, particularly evident at the early stage (Day 9). This uptake was inhibited by an ATX inhibitor, PF-8380, underscoring the specificity of the radiotracer. Conversely, [18F]FDG uptake, peaking at Day 15, decreased subsequently, likely reflective of diminished inflammation. A 2-week treatment regimen using either pirfenidone or nintedanib resulted in notable reductions of ATX expression levels and fibrosis degrees within lung tissues, based on ELISA and Masson staining, as evidenced by PET imaging with [18F]ATX-1905. [18F]FDG uptake also decreased following the treatment period. Additionally, PET/CT imaging extended to a nonhuman primate (NHP) BPF model. The uptake of [18F]ATX-1905 (SUVmax = 2.2) was significantly higher than that of [18F]FDG (SUVmax = 0.7) in fibrotic lung tissue. Using our novel ATX-specific radiotracer [18F]ATX-1905 and PET/CT imaging, we demonstrated excellent ability in early fibrosis detection, disease monitoring, and treatment assessment within lungs of the BPF mouse models. [18F]ATX-1905 displayed remarkable specificity for ATX expression and high sensitivity for ATX alterations, suggesting its potential for monitoring varying ATX expression in lungs of IPF patients.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
昏睡的南霜完成签到,获得积分10
5秒前
6秒前
ruler完成签到,获得积分10
7秒前
hhhi发布了新的文献求助10
8秒前
瓶盖发布了新的文献求助10
9秒前
12秒前
14秒前
15秒前
龚书婷发布了新的文献求助10
18秒前
儒雅香彤完成签到 ,获得积分10
18秒前
银杏完成签到,获得积分10
19秒前
詹卫卫完成签到 ,获得积分10
19秒前
贲立辉发布了新的文献求助10
20秒前
24秒前
Tianji发布了新的文献求助10
27秒前
29秒前
梅倪完成签到,获得积分10
32秒前
32秒前
烟花应助Tianji采纳,获得10
33秒前
爆米花应助发粪涂墙采纳,获得10
34秒前
儒雅致远发布了新的文献求助10
34秒前
35秒前
36秒前
DT发布了新的文献求助10
38秒前
水之冬发布了新的文献求助10
40秒前
灰原哀发布了新的文献求助10
41秒前
41秒前
44秒前
0000完成签到 ,获得积分10
45秒前
Linbo发布了新的文献求助10
46秒前
Tianji完成签到,获得积分20
47秒前
发粪涂墙发布了新的文献求助10
48秒前
keplek完成签到 ,获得积分10
50秒前
51秒前
阿烨完成签到,获得积分10
52秒前
一只半夏完成签到,获得积分10
52秒前
54秒前
思源应助Nowind采纳,获得10
58秒前
YY完成签到,获得积分20
59秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
Aktuelle Entwicklungen in der linguistischen Forschung 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989918
求助须知:如何正确求助?哪些是违规求助? 3532013
关于积分的说明 11255831
捐赠科研通 3270829
什么是DOI,文献DOI怎么找? 1805053
邀请新用户注册赠送积分活动 882233
科研通“疑难数据库(出版商)”最低求助积分说明 809216