Apoptotic PET Imaging of Rat Pulmonary Fibrosis with Small-Molecule Radiotracer.

Purpose: The purpose of this study was to assess the potential utility of small-molecule apoptotic radiotracer, 2-(5-[F]fluoropentyl)-2-methyl malonic acid ([F]ML-10), for positron emission tomography (PET)/computed tomography (CT) monitoring the progression of pulmonary fibrosis in a rat model.

Procedures: Male Sprague-Dawley rats were used to establish a rat model of pulmonary fibrosis by means of bleomycin (BLM) administration; control rats received saline (n = 12 per group). PET/CT with [F]ML-10 and 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) was performed in two groups at different stages of pulmonary fibrosis. The fibrotic response and the cell apoptosis were assessed with histologic examination. Differences in the apoptosis rate, fibrotic activity, and the lung uptake of [F]ML-10 and [F]FDG between two groups were determined with Student t test.

Results: Compared with control group, BLM group showed a higher lung uptake of [F]ML-10 at all imaging time points (all P < 0.001). During the fibrotic phase of this disease model (days 21 and 28), the lung uptake of [F]ML-10 was higher than that of [F]FDG in the BLM group (all P < 0.001). Moreover, accumulation of [F]ML-10 in the lung tissues increased in proportion to the apoptosis rate (R = 0.9863, P < 0.0001) and fibrotic activity (R = 0.9631, P < 0.0001) of rat pulmonary fibrosis. Conversely, no correlation between [F]FDG uptake and fibrotic activity was found.

Conclusions: [F]ML-10 PET/CT enabled monitoring the progression of rat pulmonary fibrosis, whereas [F]FDG PET/CT could not. Implications for noninvasive diagnosis of pulmonary fibrosis, assessment of fibrotic activity, and evaluation of antifibrotic therapy are expected.