Cell death PET/CT imaging of rat hepatic fibrosis with 18F-labeled small molecule tracer

Abstract

Purpose: To evaluate the potential feasibility of Al[¹⁸F]F-1,4,7-triazacyclononane-1,4,7-triaceticacid (NOTA)-tripolyethylene glycol (PEG₃)-Duramycin (Al[¹⁸F]F-NOTA-PEG₃-Duramycin) positron emission tomography (PET) for imaging of rat hepatic fibrosis.

Procedures: Hepatic fibrosis rat models were injected with thioacetamide (TAA), control rats received saline (n = 12 per group). Rats in the two groups underwent PET imaging using Al[¹⁸F]F-NOTA-PEG₃-Duramycin and [¹⁸F]FDG at multiple time points (2, 4, 6, and 8 weeks after TAA or saline treatment). Between-group differences in the apoptosis rate, fibrotic activity, and liver uptake of Al[¹⁸F]F-NOTA-PEG₃-Duramycin or [¹⁸F]FDG were assessed using Student's t-test. Imaging results were cross-validated using histopathology detection and Pearson's correlation test was used to assess the association relationships between radioactive uptake value and quantified histopathological data.

Results: Compared with control group at multiple time points, each TAA group showed a higher radioactive liver uptake of Al[¹⁸F]F-NOTA-PEG₃-Duramycin (each P < 0.05). Furthermore, the increase in the liver uptake of Al[¹⁸F]F-NOTA-PEG₃-Duramycin was proportional to the progression of fibrosis (R² = 0.8846, P < 0.001) and apoptosis rate (R² = 0.9208, P < 0.001) in the TAA group. Meanwhile, there were also between-group differences in [¹⁸F]FDG uptake in each phase (P < 0.05), however, no relationship between [¹⁸F]FDG uptake and the fibrotic activity was observed.

Conclusions: Al[¹⁸F]F-NOTA-PEG₃-Duramycin PET/CT could be applied to monitor the progression of liver fibrosis, whereas [¹⁸F]FDG PET/CT could not. Implications of this work for noninvasive diagnosis of liver fibrosis, assessment of fibrotic activity, and evaluation of antifibrotic therapy are expected.

Keywords: Cell death; Diagnosis; Fibrosis; Liver; Positron emission tomography.