Bae Seong-Woo, Berlth Felix, Jeong Kyoung-Yun, Suh Yun-Suhk, Kong Seong-Ho, Lee Hyuk-Joon, Kim Woo Ho, Chung June-Key, Yang Han-Kwang
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Surgery, Seoul National University Hospital, Seoul, Korea.
J Gastric Cancer. 2020 Mar;20(1):60-71. doi: 10.5230/jgc.2020.20.e7. Epub 2020 Feb 21.
The utility of 18-fluordesoxyglucose positron emission tomography ([F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake.
Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake.
Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049).
This preclinical gastric cancer PDX based [F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.
18-氟脱氧葡萄糖正电子发射断层扫描（[F]-FDG-PET）联合计算机断层扫描或磁共振成像（MRI）在胃癌中的应用仍存在争议，因此需要一种患者选择的理论依据。本研究旨在建立一种基于临床前患者来源异种移植（PDX）的胃癌[F]-FDG-PET/MRI方案，并比较不同PDX模型在肿瘤生长和FDG摄取方面的差异。
将雌性BALB/c裸鼠原位和皮下植入胃癌PDX。[F]-FDG-PET/MRI扫描方案评估包括不同肿瘤大小、FDG剂量、扫描间隔和器官特异性摄取。比较了原位和异位肿瘤植入方法下相似PDX病例的FDG亲和力。进行了显微镜和免疫组织化学研究以确认肿瘤生长，并将糖酵解标志物葡萄糖转运蛋白1（GLUT1）和己糖激酶2（HK2）与FDG摄取相关联。
器官特异性摄取分析显示肿瘤组织具有特定的FDG亲和力。确定标准扫描方案包括150μCi FDG注射剂量并在一小时后进行扫描。异位和原位植入小鼠的比较显示，原位模型的生长间隔较长，但在相似的PDX组织中摄取较高。肿瘤细胞中GLUT1和HK2表达的H评分与测量的最大标准化摄取值相关（GLUT1：Pearson r = 0.743，P = 0.009；HK2：Pearson r = 0.605，P = 0.049）。
这种基于临床前胃癌PDX的[F]-FDG-PET/MRI方案揭示了肿瘤特异性FDG摄取，并显示出与葡萄糖代谢蛋白的相关性。我们的研究结果提供了一种可应用于胃癌转化研究的PET/MRI PDX模型。
