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

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.

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.

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.

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.