Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT

Summary

This protocol describes the value of dual energy CT and PET/CT imaging methods in tumor imaging and efficacy evaluation. This article demonstrates the research methods and results acquired by dual energy CT and PET/CT to evaluate the gene regulation and targeted treatment of gastric cancer peritoneal metastasis.

Abstract

Gastric cancer remains fourth in cancer incidence worldwide with a five-year survival of only 20%-30%. Peritoneal metastasis is the most frequent type of metastasis that accompanies unresectable gastric cancer and is a definitive determinant of prognosis. Preventing and controlling the development of peritoneal metastasis could play a role in helping to prolong the survival of gastric cancer patients. A non-invasive and efficient imaging technique will help us to identify the invasion and metastasis process of peritoneal metastasis and to monitor the changes in tumor nodules in response to treatments. This will enable us to obtain an accurate description of the development process and molecular mechanisms of gastric cancer. We have recently described experiment using dual energy CT (DECT) and positron emission tomography/computed tomography (PET/CT) platforms for the detection and monitoring of gastric tumor metastasis in nude mice models. We have shown that weekly continuous monitoring with DECT and PET/CT can identify dynamic changes in peritoneal metastasis. The sFRP1-overexpression in gastric cancer mice models showed positive radiological performance, a higher FDG uptake and increasing enhancement, and the SUV_max (standardized uptake value) of nodules demonstrated an obvious alteration trend in response to targeted therapy of TGF-β1 inhibitor. In this article, we described the detailed non-invasive imaging procedures to conduct more complex research on gastric cancer peritoneal metastasis using animal models and provided representative imaging results. The use of non-invasive imaging techniques should enable us to better understand the mechanisms of tumorigenesis, monitor tumor growth, and evaluate the effect of therapeutic interventions for gastric cancer.

Introduction

Gastric cancer (GC) remains the fourth most common malignancy and the second-leading cause of cancer mortality worldwide¹. Although the accuracy in diagnosis and treatment of gastric cancer has been greatly improved, peritoneal metastasis is the most key point of gastric cancer prognosis or recurrence and is a definitive determinant of postoperative death². It is generally accepted that peritoneal dissemination is a life-threatening mode of metastasis, wherein the disease becomes uncontrollable and the prognosis of the patient is poor once peritoneal dissemination is established. Therefore, the detection and therapeutic ....

Protocol

This work was performed in strict accordance with the standards established by the Guidelines for the Care and Use of Laboratory Animals of Shanghai Jiao Tong University and was approved by the laboratory Animal Ethics Committee of Ruijin Hospital.

1. Gastric Cancer Peritoneal Metastasis Animal Model

1. Divide a moderately differentiated SGC-7901 human gastric cancer cell line into an SGC-7901/sFRP1 group and an SGC-7901/vector group. Culture the two groups of cells separately in RPMI 1640 supplemented with 10% fetal bovine serum, 100 units/mL streptomycin, and 100 µg/mL penicillin at 37 °C in a humidified atmosphere with....

Results

DECT and PET/CT scanning were performed on nude mice after two weeks of cell line injections. GSI images yielded excellent results for displaying subcutaneous metastasis beyond the contour of the abdomen for the sFRP1 overexpression group, and metastasis with peripheral enhancement was confirmed by color-scale image (Figure 1a-c). PET/CT images depicted focally abnormal FDG uptake of metastasis, including in the peritoneal and subcutaneous me.......

Discussion

Animal models have been used widely in the study of molecular mechanisms underlying gastric cancer, and to experiment with various therapeutic strategies^23,24,25. In this study, we have described a detailed protocol for gastric cancer peritoneal metastasis nude mice modeling, using DECT and PET/CT to image gastric tumors for identifying tumor cell proliferation in real-time, and monitoring peritoneal metastasis and responses to .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Iohexol	BEJING BEILU PHARMACEUTICAL CO,LTD	NMPN:H20053800	non-ionic contrast medium for DECT scan
normal saline	HUNAN KELUN PHARMACEUTICAL CO,LTD	NMPN:H43020455	placebo of control group
BALB/c nude mice	SLAC LABORATORY ANIMAL	BALB/cASlac-nu	animal model
SGC-7901  cells	Library of typical culture of Chinese academy of sciences	TCHu 46	gastric cancer cell
SB431542	Selleck	No.S1067	TGF-β1 inhibitor
GE Discovery CT750 HD	GE Healthcare		dual-energy spectral CT scanner
AW Volumeshare5	GE Healthcare		dual-energy spectral CT workstation
Siemens Inveon micro-PET/CT	Siemens Preclinical Solution		positron emission tomography/ computed tomography scanner
Inveon Acquisition Workplace	Siemens Preclinical Solution		PET-CT workstation