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Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Apoptotic PET Imaging of Rat Pulmonary Fibrosis with Small-Molecule Radiotracer
Ying Xiong1, Dahong Nie1, Shaoyu Liu1
1Department of Medical Imaging and Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, China.
Purpose:
The purpose of this study was to assess the potential utility of small-molecule apoptotic radiotracer, 2-(5-[18F]fluoropentyl)-2-methyl malonic acid ([18F]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 [18F]ML-10 and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]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 [18F]ML-10 and [18F]FDG between two groups were determined with Student t test.
Results:
Compared with control group, BLM group showed a higher lung uptake of [18F]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 [18F]ML-10 was higher than that of [18F]FDG in the BLM group (all P < 0.001). Moreover, accumulation of [18F]ML-10 in the lung tissues increased in proportion to the apoptosis rate (R2 = 0.9863, P < 0.0001) and fibrotic activity (R2 = 0.9631, P < 0.0001) of rat pulmonary fibrosis. Conversely, no correlation between [18F]FDG uptake and fibrotic activity was found.
Conclusions:
[18F]ML-10 PET/CT enabled monitoring the progression of rat pulmonary fibrosis, whereas [18F]FDG PET/CT could not. Implications for noninvasive diagnosis of pulmonary fibrosis, assessment of fibrotic activity, and evaluation of antifibrotic therapy are expected.
Insights
Small-molecule apoptotic radiotracer [18F]ML-10 PET/CT effectively monitors pulmonary fibrosis progression in rats. Unlike [18F]FDG PET/CT, [18F]ML-10 uptake correlates with fibrotic activity and apoptosis.
Area of Science:
- Nuclear medicine
- Radiochemistry
- Pulmonary medicine
Background:
- Pulmonary fibrosis is a progressive lung disease.
- Accurate monitoring of disease progression is crucial for patient management.
- Current imaging techniques have limitations in assessing fibrotic activity.
Purpose of the Study:
- To evaluate the utility of the small-molecule apoptotic radiotracer 2-(5-[18F]fluoropentyl)-2-methyl malonic acid ([18F]ML-10) for positron emission tomography/computed tomography (PET/CT) in monitoring pulmonary fibrosis progression.
- To compare the efficacy of [18F]ML-10 PET/CT with [18F]FDG PET/CT in a rat model of pulmonary fibrosis.
Main Methods:
- A rat model of pulmonary fibrosis was induced using bleomycin (BLM).
- PET/CT imaging was performed using [18F]ML-10 and [18F]FDG at different stages of fibrosis.
- Histologic examination assessed fibrotic response and apoptosis.
- Statistical analysis (Student t-test) compared imaging uptake and biologic markers.
Main Results:
- BLM-treated rats showed significantly higher lung uptake of [18F]ML-10 compared to controls at all time points (P < 0.001).
- [18F]ML-10 lung uptake was higher than [18F]FDG uptake during the fibrotic phase (P < 0.001).
- Accumulation of [18F]ML-10 strongly correlated with apoptosis rate (R2 = 0.9863) and fibrotic activity (R2 = 0.9631).
- [18F]FDG uptake did not correlate with fibrotic activity.
Conclusions:
- [18F]ML-10 PET/CT is a valuable tool for monitoring the progression of pulmonary fibrosis in a rat model.
- [18F]ML-10 PET/CT demonstrated superior performance compared to [18F]FDG PET/CT for assessing fibrotic activity.
- This tracer holds promise for noninvasive diagnosis, assessment of fibrotic activity, and evaluation of antifibrotic therapies.
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