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

OBJECTIVE: To investigate the value of 2-(3-[(18)F]fluoropropyl)-2-methyl-malonic acid ([(18)F]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 [(18)F]ML-8 or (18)F-fluorodeoxyglucose ([(18)F]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 [(18)F]ML-8 than control rats (P < .05). In BLM-treated rats, the lung to muscle relative uptake ratio of [(18)F]ML-8 was also higher than that of [(18)F]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-[(18)F]fluoropropyl)-2-methyl-malonic acid PET/CT could be used for noninvasive diagnosis of pulmonary fibrosis in a rat model.