Cis-4-[18F]fluoro-L-proline PET/CT molecular imaging quantifying liver collagenogenesis: No existing fibrotic deposition in experimental advanced-stage alcoholic liver fibrosis

Background and purpose Heavy alcohol drinking-induced alcoholic fatty liver, steatohepatitis, early-stage liver fibrosis may progress to advanced-stage (AALF)/cirrhosis. The lack of non-invasive imaging techniques for the diagnosising collagenogenesis in activated hepatic stellate cells (HSCs) can lead incurable at early reversible stage. Proline has been known as most abundant amino acid collagen type 1 synthesized by HSC with transportation proline transporter. cis -4-[ 18 F]fluoro-L-proline ([ F]proline) was reported a useful tool quantify experimental steatohepatitis. This study aims use [ F]proline micro PET AALF. Methods AALF model set up modified Lieber-DeCarli liquid ethanol diet 12 weeks along intraperitoneal injection (IP) CCl 4 (0.5 ml/kg) between 5th 12th weeks. Controls were fed an isocaloric IP. PBS. In vitro 3 H]proline uptake HSCs isolated from livers quantified using scintillation counter. Collagen production culture medium assayed ELISA. Ex vivo transporter protein compared rats ( n = 8) mice 8). H]Proline specificity ex tissues tested unlabeled inhibitor benztropine different doses. Liver H&E, trichrome stain, blood biochemistry mice. , varying times after instillation, dynamic static PET/CT done tracer 3). Correlation among collagen, SUVmax, normalized liver-to-brain ratio, liver-to-thigh fluoro-proline-induced levels analyzed. Results showed significant higher (23007.9 ± 5089.2 vs. 1075.4 119.3 CPM/mg, p < 0.001) than controls so (24.3 5.8 3.0 0.62 mg/ml, medium. Highly positive correlation found r value 0.92, 0.01). tissue no difference (14.83 5.35 mg/g) (12.91 3.62 mg/g, > 0.05), expression (7.76 1.92-fold) (6.80 0.97-fold). Unlabeled fluoro-proline induced generation specifically blocked inhibitor. SUVmax (4.90 0.91 vs . 1.63 0.38, 0.01), liver/brain ratio (12.54 0.72 2.33 0.41, liver/thigh (6.03 0.78 1.09 0.09, 0.01) controls, which are all positively correlated ≥ 0.93, mice, but not existing collagen. histology increased Blood serum ALT AST remarkably there is fibrotic parameters HA, A2M, TGFβ1, MMP1. Conclusions might be visualize fails potential sensitivity assess activity severity fibrosis.