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

Purpose: To evaluate the potential feasibility of Al[F-18]F-1,4,7- triazacyclononane- 1,4,7-triaceticacid (NOTA)-tripolyethylene glycol (PEG3)-Duramycin (Al[F-18]F-NOTA-PEG3-Duramycin) positron emission tomography (PET) for imaging of rat hepatic fibrosis. Procedures: Hepatic fibrosis ratmodels were injected with thioacetamide (TAA), control rats received saline (n= 12 per group). Rats in the two groups underwent PET imaging using Al[F-18]F-NOTA-PEG3-Duramycin and [F-18] 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[F-18]F-NOTA-PEG3-Duramycin or [F-18]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[F-18]F-NOTA-PEG3-Duramycin (each P< 0.05). Furthermore, the increase in the liver uptake of Al[F-18] F-NOTA-PEG3-Duramycin was proportional to the progression of fibrosis (R-2= 0.8846, P < 0.001) and apoptosis rate (R-2= 0.9208, P < 0.001) in the TAA group. Meanwhile, there were also between-group differences in [F-18] FDG uptake in each phase (P < 0.05), however, no relationship between [F-18]FDG uptake and the fibrotic activity was observed. Conclusions: Al[F-18]F-NOTA-PEG3-Duramycin PET/CT could be applied to monitor the progression of liver fibrosis, whereas [F-18]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. (C) 2021 Elsevier Inc. All rights reserved.