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2000
Volume 20, Issue 1
  • ISSN: 1573-4056
  • E-ISSN: 1875-6603
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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 experiment. Collagen type 1 production was tested by ELISA in a culture medium. The expression of type 1 collagen and proline transporters in experiments was compared between ALF rats and mice. Different doses of unlabeled proline and benztropine were quantified [3H]proline in liver tissues. Tracer uptake in different organs including the liver in ALF and control mice 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 , the mouse-to-rat model was compared. Type 1 collagen levels of ALF mice liver tissue in 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. [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.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Quantification of Collagenogenesis in Experimental Early-stage Alcoholic Liver Fibrosis using Cis-4-[18F]fluoro-L-Proline microPET
Curr. Med. Imaging 20, e250823220367 (2024); https://doi.org/10.2174/1573405620666230825113455
/content/journals/cmir/10.2174/1573405620666230825113455
/content/journals/cmir/10.2174/1573405620666230825113455
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  • Article Type:     Research Article
Keyword(s): Cis-4-[18F]fluoro-L-proline; Collagenogenesis; Early-stage alcoholic liver fibrosis; Hepatic stellate cells; Molecular imaging; PET/CT

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