Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Department of Nuclear Engineering, University of California, Berkeley, CA, USA.
Mol Imaging. 2022 Jul 25;2022:5185951. doi: 10.1155/2022/5185951. eCollection 2022.
Quantitative [F]-(2S,4R)4-fluoroglutamine ([F]4-FGln or more simply [F]FGln) metabolic kinetic parameters are compared with activity levels of glutamine metabolism in different types of hepatocellular carcinoma (HCC).
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 [F]FGln PET data were acquired and reconstructed for fasted MYC mice ( = 11 tumors from 7 animals), fasted MET mice ( = 8 tumors from 6 animals), fasted FVBN controls ( = 8 normal liver regions from 6 animals), nonfasted MYC mice ( = 16 tumors from 6 animals), and nonfasted FVBN controls ( = 8 normal liver regions from 3 animals). The influx rate constants ( ) using the one-tissue compartment model were derived for each tumor with the left ventricular blood pool input function.
Influx rate constants were significantly higher for MYC tumors ( = 0.374 ± 0.133) than for MET tumors ( = 0.141 ± 0.058) under fasting conditions ( = 0.0002). Rate constants were also significantly lower for MET tumors ( = 0.141 ± 0.135) than normal livers ( = 0.332 ± 0.179) under fasting conditions ( = 0.0123). Fasting conditions tested for MYC tumors and normal livers did not result in any significant difference with values > 0.005.
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 [F]FGln PET imaging as a tool to assess glutamine metabolism in HCC tumors with a caution that it may not be able to clearly distinguish HCC tumors from normal liver tissue.
定量 [F]-(2S,4R)4-氟谷氨酸 ([F]4-FGln，简称 [F]FGln) 代谢动力学参数与不同类型肝细胞癌 (HCC) 中的谷氨酰胺代谢活性水平进行比较。
在这项研究中，我们使用了两种由原癌基因 MYC 和 MET 诱导的 HCC 转基因小鼠模型。生化数据表明，与 MET 诱导的肿瘤相比，MYC 诱导的肿瘤中谷氨酰胺代谢水平升高。对禁食 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（=6 只动物的 8 个正常肝区）、非禁食 MYC 小鼠（=6 只动物的 16 个肿瘤）和非禁食 FVBN 对照（=3 只动物的 8 个正常肝区）进行了 1 小时动态 [F]FGln PET 数据采集和重建。使用单室模型从每个肿瘤中得出流入率常数 ( )，以左心室血池输入函数为参考。
在禁食条件下，MYC 肿瘤的流入率常数明显高于 MET 肿瘤（ =0.374 ± 0.133）（ =0.0002）。在禁食条件下，MET 肿瘤的常数（ =0.141 ± 0.135）也明显低于正常肝脏（ =0.332 ± 0.179）（ =0.0123）。在禁食条件下，对 MYC 肿瘤和正常肝脏进行检测， 值均 >0.005，未得出任何显著差异。
较高的流入率常数对应于生化测定确定的较高谷氨酰胺代谢水平。数据表明，MYC 和 MET 肿瘤之间的谷氨酰胺代谢存在明显差异。我们的研究表明，[F]FGln PET 成像作为评估 HCC 肿瘤中谷氨酰胺代谢的工具具有潜力，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。
