Apoptotic PET Imaging of Rat Pulmonary Fibrosis With [18F]ML-8.

Ying Xiong,Shaoyu Liu,Xianhong Xiang,Jing Zhao,Shu Su,Zhanwen Zhang,Ganghua Tang,Aixia Sun,Hui Ma,Dahong Nie

doi:10.1177/1536012118795728

Abstract

Objective:To investigate the value of 2-(3-[18F]fluoropropyl)-2-methyl-malonic acid ([18F]ML-8) positron emission tomography (PET) imaging of rat pulmonary fibrosis.Methods:Male Sprague-Dawley rats were divided into 2 groups, including pulmonary fibrosis model group and control group. The rat model was established by an intratracheal instillation of bleomycin (BLM). Control rats were treated with saline. Positron emission tomography/computed tomography (CT) with [18F]ML-8 or 18F-fluorodeoxyglucose ([18F]FDG) was performed on 2 groups. After PET/CT imaging, lung tissues were collected for histologic examination. Data were analyzed and comparisons between 2 groups were performed using Student t test.Results:Bleomycin-treated rats showed a higher lung uptake of [18F]ML-8 than control rats (P < .05). In BLM-treated rats, the lung to muscle relative uptake ratio of [18F]ML-8 was also higher than that of [18F]FDG (P < .05). Pathological examination showed overproliferation of fibroblasts and deposition of collagen in lungs from BLM-treated rats. Compared to control rats, BLM-treated rats had higher lung hydroxyproline content (P < .05). Immunofluorescence staining indicated more apoptotic cells in BLM-treated rats than those in control rats. Moreover, the apoptosis rate of lung tissues obtained from BLM-treated rats was higher than that from control rats (P < .05).Conclusions:2-(3-[18F]fluoropropyl)-2-methyl-malonic acid PET/CT could be used for noninvasive diagnosis of pulmonary fibrosis in a rat model.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic interstitial lung disease with unclear cause
After positron emission tomography (PET)/computed tomography (CT) scans, these rats were sacrificed under deep anesthesia, and lung tissues were collected for further histopathological analysis
Idiopathic pulmonary fibrosis is induced by a variety of environmental and genetic factors, which result in repetitive type II alveolar epithelial cell injury and abnormal lung repair processes, proliferation of fibroblasts, and excessive accumulation of extracellular matrix proteins, which leads to destruction of the lung architecture and severe insufficient pulmonary functions.[5,26,27]

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic interstitial lung disease with unclear cause. Inflammation is present in lung tissues of patients with IPF, it doesn’t seem to play an important role in the pathogenesis of pulmonary fibrosis as anti-inflammatory treatments have been shown to be ineffective. Patients with IPF have a poor prognosis, with a 5-year mortality rate above 50% and a median survival of 2 to 5 years.[1,5] The current modality of pulmonary fibrosis diagnosis remains high-resolution computed tomography (HRCT) and lung biopsy. High-resolution computed tomography shows the changes of lung density but can’t provide functional imaging information of IPF, such as disease activity.[7,8] Compared to HRCT, positron emission tomography (PET)/CT provides both structural and functional imaging

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Conclusion