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
刚刚
xinxiangshicheng完成签到 ,获得积分10
1秒前
愤怒的小鸟完成签到,获得积分10
1秒前
MY完成签到,获得积分10
1秒前
顾矜应助lenetivy采纳,获得10
2秒前
自觉寒梦发布了新的文献求助10
2秒前
美好斓发布了新的文献求助10
2秒前
郑文涛完成签到,获得积分10
3秒前
JamesPei应助专注的白柏采纳,获得10
4秒前
YHY发布了新的文献求助10
6秒前
好吃发布了新的文献求助10
6秒前
拾光完成签到,获得积分10
7秒前
long完成签到 ,获得积分10
7秒前
天天向上发布了新的文献求助10
8秒前
6260完成签到,获得积分10
8秒前
pcr163应助linhanwenzhou采纳,获得50
9秒前
9秒前
酷酷元风完成签到,获得积分10
10秒前
11秒前
天才幸运鱼完成签到,获得积分10
11秒前
12秒前
12秒前
粥游天下完成签到,获得积分10
13秒前
jcc完成签到,获得积分10
13秒前
哈哈哈哈完成签到,获得积分10
13秒前
lighthouse完成签到,获得积分10
14秒前
平凡中的限量版完成签到,获得积分10
14秒前
大伟完成签到,获得积分10
14秒前
long关注了科研通微信公众号
15秒前
懵懂的毛豆完成签到,获得积分10
15秒前
zzcherished发布了新的文献求助10
15秒前
zyq发布了新的文献求助10
15秒前
我是老大应助哦哦哦采纳,获得10
16秒前
YHY完成签到,获得积分10
16秒前
16秒前
天天呼的海角完成签到,获得积分10
19秒前
量子星尘发布了新的文献求助10
22秒前
22秒前
22秒前
jiangcai完成签到,获得积分10
23秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
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 4038368
求助须知:如何正确求助?哪些是违规求助? 3576068
关于积分的说明 11374313
捐赠科研通 3305780
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029