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

Mol Imaging. 2018 Jan-Dec:17:1536012118795728. 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.

Keywords: PET/CT; [18F]FDG; [18F]ML-8; diagnosis; pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Fluorodeoxyglucose F18 / chemistry
  • Lung / diagnostic imaging
  • Lung / pathology
  • Male
  • Methylmalonic Acid / analogs & derivatives*
  • Methylmalonic Acid / chemistry
  • Positron Emission Tomography Computed Tomography
  • Positron-Emission Tomography*
  • Pulmonary Fibrosis / diagnostic imaging*
  • Pulmonary Fibrosis / pathology*
  • Rats, Sprague-Dawley

Substances

  • 2-(3-fluoropropyl)-2-methylmalonic acid
  • Fluorodeoxyglucose F18
  • Methylmalonic Acid