J Gastric Cancer.  2020 Mar;20(1):60-71. 10.5230/jgc.2020.20.e7.

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

Affiliations
  • 1Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. hkyang@snu.ac.kr
  • 2Department of Surgery, Seoul National University Hospital, Seoul, Korea.
  • 3Department of General, Visceral and Transplant Surgery, University of Mainz, Mainz, Germany.
  • 4Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
  • 5Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.

Abstract

PURPOSE
The utility of 18-fluordesoxyglucose positron emission tomography ([¹â¸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 [¹â¸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. [¹â¸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 [¹â¸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.

Keyword

Xenograft; PET scan; Glycolysis; Gastric cancer

MeSH Terms

Animals
Female
Glucose
Glucose Transport Proteins, Facilitative
Glycolysis
Heterografts
Hexokinase
Humans
Magnetic Resonance Imaging
Mice
Patient Selection
Positron-Emission Tomography
Stomach Neoplasms*
Glucose
Glucose Transport Proteins, Facilitative
Hexokinase
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