Establishment of a [¹⁸F]-FDG-PET/MRI Imaging Protocol for Gastric Cancer PDX as a Preclinical Research Tool

Abstract

Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([ 18 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 [ 18 F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [ 18 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. Results: 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). Conclusions: This preclinical gastric cancer PDX based [ 18 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.

Magnetic Fields and Cancer: Epidemiology, Cellular Biology, and Theranostics

“…MRI is more accurate in achieving adequate staging results [369,370] and in the evaluation of T-stage than CT [371,372]. DCE-MRI parameters of gastric cancers may provide prognostic information [373,374], whereas multiparametric fully integrated 18 fluordesoxyglucose ([F-18]-FDG)-PET/MRI may improve the diagnostic accuracy for translational gastric cancer research [375], for preoperative M staging as well as the resectability of gastric cancers compared to multi detector computed tomography (MDCT) [376]. Compared with PET/CT, PET/MRI performs more accurately in TNM staging and is optimal for accurate N staging [377], whereas high-resolution MRI (HR MRI) has good diagnostic performance and may serve as an alternative technique in the T staging of patients with esophagogastric junction cancer in clinical practice [378].…”

Glucose metabolic profiles evaluated by PET associated with molecular characteristic landscape of gastric cancer

“…Six-week-old female BALB/c nu/nu mice (Orient Bio., Sungnam, Korea) were used to establish PDX tumor mouse models (n = 3 per PDX case). The mouse tumor modeling, small animal [ 18 F]FDG PET/MR imaging, and analysis were conducted as previously described [11]. All procedures involving in-vivo mouse studies were approved by the Institutional Animal Care and Use Committee (IACUC) at Seoul National University and complied with the Guide for the Care and Use of Laboratory Animals (SNU-170704-3).…”