Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models.

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models.
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I型胶原蛋白靶向PET探针,用于临床前模型中的肺纤维化检测和分期。

DOI:
10.1126/scitranslmed.aaf4696
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发表时间:
2017-04-05
影响因子:
17.1
通讯作者:
Caravan P
Caravan P
中科院分区:
医学1区
文献类型:
--
作者:
Désogère P;Tapias LF;Hariri LP;Rotile NJ;Rietz TA;Probst CK;Blasi F;Day H;Mino-Kenudson M;Weinreb P;Violette SM;Fuchs BC;Tager AM;Lanuti M;Caravan P

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肺纤维化是一种肺部瘢痕形成,可由放射损伤、药物毒性、环境或遗传原因以及未知原因引起[特发性肺纤维化(IPF)]。胶原蛋白的过度表达是器官纤维化的标志。在这里,我们描述了一种基于肽的PET探针(68 Ga-CBP 8),靶向胶原蛋白I型。我们在博来霉素诱导的肺纤维化小鼠模型中体内评估了68 Ga-CBP 8。68 Ga-CBP 8在患病动物中显示出对肺纤维化的高特异性和高靶:背景比率。肺PET信号和肺68 Ga-CBP 8摄取(离体定量)与患有纤维化的小鼠中的肺胶原蛋白的量线性相关(r2=0.80)。我们进一步证明,68 Ga-CBP 8探针可用于监测与血管渗漏相关的肺纤维化的第二小鼠模型中对治疗的反应。IPF患者肺组织的离体分析支持动物结果。这些研究表明,68 Ga-CBP 8是人类肺纤维化非侵入性成像的有希望的候选者。
Pulmonary fibrosis is a scarring of the lungs that can arise from radiation injury, drug toxicity, environmental or genetic causes, and for unknown reasons [idiopathic pulmonary fibrosis (IPF)]. Overexpression of collagen is a hallmark of organ fibrosis. Here, we describe a peptide-based PET probe (68Ga-CBP8) that targets collagen type I. We evaluated 68Ga-CBP8 in vivo in the bleomycin-induced mouse model of pulmonary fibrosis. 68Ga-CBP8 showed high specificity for pulmonary fibrosis and high target:background ratios in diseased animals. The lung PET signal and lung 68Ga-CBP8 uptake (quantified ex vivo) correlated linearly (r2=0.80) with the amount of lung collagen in mice with fibrosis. We further demonstrated that the 68Ga-CBP8 probe could be used to monitor response to treatment in a second mouse model of pulmonary fibrosis associated with vascular leak. Ex vivo analysis of lung tissue from patients with IPF supported the animal findings. These studies indicate that 68Ga-CBP8 is a promising candidate for non-invasive imaging of human pulmonary fibrosis.
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