[¹⁸F]-(2S,4R)4-Fluoroglutamine PET Imaging of Glutamine Metabolism in Murine Models of Hepatocellular Carcinoma (HCC).

IF 2.2 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular Imaging Pub Date : 2022-07-25 eCollection Date: 2022-01-01 DOI:10.1155/2022/5185951

Youngho Seo, Miranda C Craig, Stephanie T Murphy, Jinjin Feng, Xin Chen, Mariia Yuneva

{"title":"[18F]-(2S,4R)4-Fluoroglutamine PET Imaging of Glutamine Metabolism in Murine Models of Hepatocellular Carcinoma (HCC).","authors":"Youngho Seo, Miranda C Craig, Stephanie T Murphy, Jinjin Feng, Xin Chen, Mariia Yuneva","doi":"10.1155/2022/5185951","DOIUrl":null,"url":null,"abstract":"Purpose: Quantitative in vivo [18F]-(2S,4R)4-fluoroglutamine ([18F]4-FGln or more simply [18F]FGln) metabolic kinetic parameters are compared with activity levels of glutamine metabolism in different types of hepatocellular carcinoma (HCC).Methods: For this study, we used two transgenic mouse models of HCC induced by protooncogenes, MYC, and MET. Biochemical data have shown that tumors induced by MYC have increased levels of glutamine metabolism compared to those induced by MET. One-hour dynamic [18F]FGln PET data were acquired and reconstructed for fasted MYC mice (n = 11 tumors from 7 animals), fasted MET mice (n = 8 tumors from 6 animals), fasted FVBN controls (n = 8 normal liver regions from 6 animals), nonfasted MYC mice (n = 16 tumors from 6 animals), and nonfasted FVBN controls (n = 8 normal liver regions from 3 animals). The influx rate constants (K 1) using the one-tissue compartment model were derived for each tumor with the left ventricular blood pool input function.Results: Influx rate constants were significantly higher for MYC tumors (K 1 = 0.374 ± 0.133) than for MET tumors (K 1 = 0.141 ± 0.058) under fasting conditions (P = 0.0002). Rate constants were also significantly lower for MET tumors (K 1 = 0.141 ± 0.135) than normal livers (K 1 = 0.332 ± 0.179) under fasting conditions (P = 0.0123). Fasting conditions tested for MYC tumors and normal livers did not result in any significant difference with P values > 0.005.Conclusion: Higher influx rate constants corresponded to elevated levels of glutamine metabolism as determined by biochemical assays. The data showed that there is a distinctive difference in glutamine metabolism between MYC and MET tumors. Our study has demonstrated the potential of [18F]FGln PET imaging as a tool to assess glutamine metabolism in HCC tumors in vivo with a caution that it may not be able to clearly distinguish HCC tumors from normal liver tissue.","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351703/pdf/","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2022/5185951","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}

引用次数: 1

Abstract

Purpose: Quantitative in vivo [¹⁸F]-(2S,4R)4-fluoroglutamine ([¹⁸F]4-FGln or more simply [¹⁸F]FGln) metabolic kinetic parameters are compared with activity levels of glutamine metabolism in different types of hepatocellular carcinoma (HCC).

Methods: For this study, we used two transgenic mouse models of HCC induced by protooncogenes, MYC, and MET. Biochemical data have shown that tumors induced by MYC have increased levels of glutamine metabolism compared to those induced by MET. One-hour dynamic [¹⁸F]FGln PET data were acquired and reconstructed for fasted MYC mice (n = 11 tumors from 7 animals), fasted MET mice (n = 8 tumors from 6 animals), fasted FVBN controls (n = 8 normal liver regions from 6 animals), nonfasted MYC mice (n = 16 tumors from 6 animals), and nonfasted FVBN controls (n = 8 normal liver regions from 3 animals). The influx rate constants (K ₁) using the one-tissue compartment model were derived for each tumor with the left ventricular blood pool input function.

Results: Influx rate constants were significantly higher for MYC tumors (K ₁ = 0.374 ± 0.133) than for MET tumors (K ₁ = 0.141 ± 0.058) under fasting conditions (P = 0.0002). Rate constants were also significantly lower for MET tumors (K ₁ = 0.141 ± 0.135) than normal livers (K ₁ = 0.332 ± 0.179) under fasting conditions (P = 0.0123). Fasting conditions tested for MYC tumors and normal livers did not result in any significant difference with P values > 0.005.

Conclusion: Higher influx rate constants corresponded to elevated levels of glutamine metabolism as determined by biochemical assays. The data showed that there is a distinctive difference in glutamine metabolism between MYC and MET tumors. Our study has demonstrated the potential of [¹⁸F]FGln PET imaging as a tool to assess glutamine metabolism in HCC tumors in vivo with a caution that it may not be able to clearly distinguish HCC tumors from normal liver tissue.

Abstract Image

查看原文本刊更多论文

[18F]-(2S,4R)4-氟谷氨酰胺PET显像对小鼠肝细胞癌(HCC)模型谷氨酰胺代谢的影响

目的:将体内[18F]-(2S,4R)4-氟谷氨酰胺([18F]4-FGln或更简单的[18F]FGln)代谢动力学参数与不同类型肝细胞癌(HCC)中谷氨酰胺代谢活性水平进行定量比较。方法:在本研究中，我们使用了原癌基因MYC和MET诱导的两种肝癌转基因小鼠模型。生化数据表明，与MET诱导的肿瘤相比，MYC诱导的肿瘤谷氨酰胺代谢水平增加。获取并重建了禁食MYC小鼠(7只动物的11个肿瘤)、禁食MET小鼠(6只动物的8个肿瘤)、禁食FVBN对照组(6只动物的8个正常肝脏区域)、非禁食MYC小鼠(6只动物的16个肿瘤)和非禁食FVBN对照组(3只动物的8个正常肝脏区域)的1小时动态[18F]FGln PET数据。利用单组织室模型推导出每个肿瘤具有左心室血池输入功能的内流速率常数(k1)。结果:空腹条件下MYC肿瘤的内流速率常数(k1 = 0.374±0.133)显著高于MET肿瘤(k1 = 0.141±0.058)(P = 0.0002)。空腹条件下MET肿瘤的速率常数(k1 = 0.141±0.135)也显著低于正常肝脏(k1 = 0.332±0.179)(P = 0.0123)。MYC肿瘤和正常肝脏的空腹测试结果无显著差异(P值> 0.005)。结论:较高的内流速率常数与生化测定的谷氨酰胺代谢水平升高相对应。数据显示MYC和MET肿瘤的谷氨酰胺代谢存在显著差异。我们的研究已经证明了[18F]FGln PET成像作为评估HCC肿瘤体内谷氨酰胺代谢的工具的潜力，但需要注意的是，它可能无法清楚地区分HCC肿瘤与正常肝组织。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology

自引率

3.60%

发文量

期刊介绍： Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.

文献相关原料

公司名称	产品信息	采购帮参考价格