Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Jiangsu Institute of Nuclear Medicine, Wuxi, China.
Nucl Med Biol. 2019 May-Jun;72-73:36-44. doi: 10.1016/j.nucmedbio.2019.07.004. Epub 2019 Jul 11.
Positron emission tomography (PET) is extensively used in clinical oncology for tumor detection. This study aimed to explore the application of the radiotracers [F]fluorodeoxyglucose ([F]FDG), 3'-deoxy-3'- [F]fluorothymidine ([F]FLT), and [F]fluoromisonidazole ([F]FMISO) in the diagnosis and monitoring of hepatic metastasis in human colorectal cancer (CRC).
A mouse model of human CRC with hepatic metastasis was established by intrasplenic implantation of human CRC cell lines LoVo or HCT8. Metastatic potential of these two cell lines was evaluated by wound healing assay in vitro and survival analysis. Uptake of radiotracers between LoVo and HCT8 cells and uptake of radiotracers in the resulting mouse tumor models were examined by in vivo and in vitro experiments. Uptake of each radiotracer in hepatic metastatic lesions was quantified and expressed as standard uptake value (SUV). Protein expression of multiple tumor biomarkers was determined in metastatic lesions. The correlation between tracer uptake and tumor marker expression was evaluated using linear regression.
LoVo cells exhibited a stronger metastatic potential and a higher radiotracer uptake ability than HCT8 cells, as evidenced by significantly greater wound closure percentage, shorter survival, higher incidence of liver metastases, and higher cellular radiotracer levels in LoVo cells or LoVo cell-xenografted mice. SUV values of [F]FLT and [F]FMISO, but not [F]FDG, in LoVo cell-derived metastatic lesions were significantly greater than those in HCT8 lesions. Mechanistically, the expression of MACC1, HIF-1α, and GLUT-1(metastasis associated in colon cancer 1, MACC1; hypoxia-inducible factor 1-alpha, HIF-1α; and glucose transporter 1, GLUT-1, respectively) in LoVo cell-derived metastatic lesions was more effectively induced than in HCT8-derived ones. A linear regression analysis demonstrated significant positive correlations between [F]FLT/[F]FMISO uptake and tumor biomarker expression in metastatic tissues.
[F]FLT and [F]FMISO-based PET imaging may serve as a promising method for early detection and monitoring of hepatic metastasis in patients with CRC.
正电子发射断层扫描（PET）在肿瘤检测方面在临床肿瘤学中得到广泛应用。本研究旨在探讨放射性示踪剂[F]氟脱氧葡萄糖（[F]FDG）、3'-脱氧-3'-[F]氟胸苷（[F]FLT）和[F]氟米索硝唑（[F]FMISO）在人结直肠癌（CRC）肝转移诊断和监测中的应用。
通过脾内植入人 CRC 细胞系 LoVo 或 HCT8 建立人 CRC 肝转移模型。体外划痕愈合试验和生存分析评估这两种细胞系的转移潜能。通过体内和体外实验研究两种细胞系和所得小鼠肿瘤模型中放射性示踪剂的摄取情况。用标准摄取值（SUV）定量测定每种放射性示踪剂在肝转移灶中的摄取。测定转移灶中多种肿瘤标志物的蛋白表达。用线性回归评价示踪剂摄取与肿瘤标志物表达的相关性。
LoVo 细胞比 HCT8 细胞具有更强的转移潜能和更高的放射性示踪剂摄取能力，表现在 LoVo 细胞的划痕愈合百分比更大、生存时间更短、肝转移发生率更高，以及 LoVo 细胞或 LoVo 细胞异种移植小鼠的细胞放射性示踪剂水平更高。与 HCT8 病灶相比，[F]FLT 和[F]FMISO 的 SUV 值（但不是[F]FDG）在 LoVo 细胞衍生的转移病灶中明显更高。在机制上，LoVo 细胞衍生的转移病灶中 MACC1、HIF-1α 和 GLUT-1（分别为结肠癌转移相关 1（MACC1）、缺氧诱导因子 1-α（HIF-1α）和葡萄糖转运蛋白 1（GLUT-1））的表达比 HCT8 衍生的病灶更有效地诱导。线性回归分析表明，转移组织中[F]FLT/[F]FMISO 摄取与肿瘤标志物表达之间存在显著正相关。
[F]FLT 和[F]FMISO 基于 PET 成像可能成为 CRC 患者肝转移早期检测和监测的一种有前途的方法。
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