Title:Quantification of Collagenogenesis in Experimental Early-stage Alcoholic Liver
Fibrosis using Cis-4-[18F]fluoro-L-Proline microPET
Volume: 20
Author(s): Shujing Li, Hongxia Chen*, Liya Pi, Yingqi Zhang, Youseff Ali and Qi Cao*
Affiliation:
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Keywords:
Molecular imaging, PET/CT, Early-stage alcoholic liver fibrosis, Cis-4-[18F]fluoro-L-proline, Hepatic stellate cells, Collagenogenesis.
Abstract:
Purpose:
The diagnosis and quantification of early-stage alcoholic liver fibrosis (ALF) are vital and the objective is to establish a noninvasive PET technique
to quantify the collagenogenesis of hepatic stellate cells (HSC) in an ALF mouse model.
Methods:
To establish the ALF animal model, a liquid alcohol diet (8 weeks), and CCl4 were injected intraperitoneally at 5-8 weeks. A liquid scintillation
counter was used to measure [3H]proline uptake by rats HSC in vitro experiment. Collagen type 1 production was tested by ELISA in a culture
medium. The expression of type 1 collagen and proline transporters in ex vivo experiments was compared between ALF rats and mice. Different
doses of unlabeled proline and benztropine were ex vivo quantified [3H]proline in liver tissues. Tracer uptake in different organs including the liver
in ALF and control mice in vivo was quantified using [18F]fluoro-proline microPET/CT.
Results:
The optimal dose and time of [3H]proline uptake by HSC was 19-37MBq/L and 30-90min after culture. Higher [3H]proline uptake and type 1
collagen production in HSC were found in ALF and control rats. There was a high correlation between [3H]proline uptake and type 1 collagen in
ALF rats. To cut the costs of tracer usage and imaging in vivo, the mouse-to-rat model was compared. Type 1 collagen levels of ALF mice liver
tissue in ex vivo were similar to ALF rats, as was proline transporter protein. Unlabeled proline of type 1 collagen and [3H]proline uptake of ALF
mice was blocked by benztropine. in vivo [18F]fluoro-proline PET/CT imaging, SUVmax in the liver, normalized liver/brain and liver/thigh ratio
were significantly different between ALF mice and controls and there was a strong positive correlation among these three indexes in ALF mice.
Conclusion:
[18F]fluoro-proline microPET/CT is feasible to quantify collagenogenesis in HSC in early-stage ALF animal models, which may be used as a
promising and reliable noninvasive diagnostic technique.
