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Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma
BACKGROUND: De novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551611/ https://www.ncbi.nlm.nih.gov/pubmed/36237546 http://dx.doi.org/10.3389/fmed.2022.1008200 |
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author | Tsao, Chin-Ho Jhou, Rong-Hong Ke, Chien-Chih Chang, Chun-Wei Chang, Chi-Wei Yang, Bang-Hung Huang, Wen-Sheng Shih, Bing-Fu Liu, Ren-Shyan |
author_facet | Tsao, Chin-Ho Jhou, Rong-Hong Ke, Chien-Chih Chang, Chun-Wei Chang, Chi-Wei Yang, Bang-Hung Huang, Wen-Sheng Shih, Bing-Fu Liu, Ren-Shyan |
author_sort | Tsao, Chin-Ho |
collection | PubMed |
description | BACKGROUND: De novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic activity before treatment. Here, we proposed an imaging probe, positron emission tomography/computed tomography (PET/CT) with dual tracers combining (11)C-acetate and (18)F-fluorodeoxyglucose ((18)F-FDG), to assess the lipogenic activity of hepatocellular carcinoma (HCC) and predict the response to lipogenesis-targeted therapy. METHODS: We investigated the association between (11)C-acetate/(18)F-FDG uptake and de novo lipogenesis in three HCC cell lines (from well-differentiated to poorly differentiated: HepG2, Hep3B, and SkHep1) by examining the expression of lipogenic enzymes: acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN), and ATP citrate lyase (ACLY). The glycolysis level was determined through glycolytic enzymes: pyruvate dehydrogenase expression (PDH). On the basis of the findings of dual-tracer PET/CT, we evaluated the treatment response to a lipase inhibitor (orlistat) in cell culture experiments and xenograft mice. RESULTS: Dual-tracer PET/CT revealed the lipogenic activity of various HCC cells, which was positively associated with (11)C-acetate uptake and negatively associated with (18)F-FDG uptake. This finding represents the negative association between (11)C-acetate and (18)F-FDG uptake. Because these two tracers revealed the lipogenic and glycolytic activity, respectively, which implies an antagonism between lipogenic metabolism and glucose metabolism in HCC. In addition, dual-tracer PET/CT not only revealed the lipogenic activity but also predicted the treatment response to lipogenesis-targeted therapy. For example, HepG2 xenografts with high (11)C-acetate but low (18)F-FDG uptake exhibited high lipogenic activity and responded well to orlistat treatment, whereas SkHep1 xenografts with low (11)C-acetate but high (18)F-FDG uptake exhibited lower lipogenic activity and poor response to orlistat. CONCLUSION: The proposed non-invasive dual-tracer PET/CT imaging can reveal the lipogenesis and glycolysis status of HCC, thus providing an ideal imaging probe for predicting the therapeutic response of HCC to lipogenesis-targeted therapy. |
format | Online Article Text |
id | pubmed-9551611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95516112022-10-12 Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma Tsao, Chin-Ho Jhou, Rong-Hong Ke, Chien-Chih Chang, Chun-Wei Chang, Chi-Wei Yang, Bang-Hung Huang, Wen-Sheng Shih, Bing-Fu Liu, Ren-Shyan Front Med (Lausanne) Medicine BACKGROUND: De novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic activity before treatment. Here, we proposed an imaging probe, positron emission tomography/computed tomography (PET/CT) with dual tracers combining (11)C-acetate and (18)F-fluorodeoxyglucose ((18)F-FDG), to assess the lipogenic activity of hepatocellular carcinoma (HCC) and predict the response to lipogenesis-targeted therapy. METHODS: We investigated the association between (11)C-acetate/(18)F-FDG uptake and de novo lipogenesis in three HCC cell lines (from well-differentiated to poorly differentiated: HepG2, Hep3B, and SkHep1) by examining the expression of lipogenic enzymes: acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN), and ATP citrate lyase (ACLY). The glycolysis level was determined through glycolytic enzymes: pyruvate dehydrogenase expression (PDH). On the basis of the findings of dual-tracer PET/CT, we evaluated the treatment response to a lipase inhibitor (orlistat) in cell culture experiments and xenograft mice. RESULTS: Dual-tracer PET/CT revealed the lipogenic activity of various HCC cells, which was positively associated with (11)C-acetate uptake and negatively associated with (18)F-FDG uptake. This finding represents the negative association between (11)C-acetate and (18)F-FDG uptake. Because these two tracers revealed the lipogenic and glycolytic activity, respectively, which implies an antagonism between lipogenic metabolism and glucose metabolism in HCC. In addition, dual-tracer PET/CT not only revealed the lipogenic activity but also predicted the treatment response to lipogenesis-targeted therapy. For example, HepG2 xenografts with high (11)C-acetate but low (18)F-FDG uptake exhibited high lipogenic activity and responded well to orlistat treatment, whereas SkHep1 xenografts with low (11)C-acetate but high (18)F-FDG uptake exhibited lower lipogenic activity and poor response to orlistat. CONCLUSION: The proposed non-invasive dual-tracer PET/CT imaging can reveal the lipogenesis and glycolysis status of HCC, thus providing an ideal imaging probe for predicting the therapeutic response of HCC to lipogenesis-targeted therapy. Frontiers Media S.A. 2022-09-27 /pmc/articles/PMC9551611/ /pubmed/36237546 http://dx.doi.org/10.3389/fmed.2022.1008200 Text en Copyright © 2022 Tsao, Jhou, Ke, Chang, Chang, Yang, Huang, Shih and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Tsao, Chin-Ho Jhou, Rong-Hong Ke, Chien-Chih Chang, Chun-Wei Chang, Chi-Wei Yang, Bang-Hung Huang, Wen-Sheng Shih, Bing-Fu Liu, Ren-Shyan Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma |
title | Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma |
title_full | Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma |
title_fullStr | Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma |
title_full_unstemmed | Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma |
title_short | Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma |
title_sort | dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551611/ https://www.ncbi.nlm.nih.gov/pubmed/36237546 http://dx.doi.org/10.3389/fmed.2022.1008200 |
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