Name: gene regulation and targeted therapy in gastric cancer peritoneal metastasis: radiological findings from dual energy ct and pet/ct
Uploaded: 2018-01-22T14:00:00
Description: Watch this Scientific Journal Video about Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT at JoVE.com

This work was supported by the NSFC (No. U1532107) and Shanghai Jiao Tong University Biomedical Engineering project (No. YG2014MS53). The authors would like to acknowledge Jianying Li and Yan Shen for their helpful comments and technical support efforts in developing the DECT and PET/CT imaging method.

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
<ol>
	<li>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...

<ol>
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Animal models have been used widely in the study of molecular mechanisms underlying gastric cancer, and to experiment with various therapeutic strategies23,24,25. 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 ...

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 effect evaluation of gastric cancer peritoneal metastasis is crucial for clinical practice.
The increasing incidence and mortality of gastric cancer had spurred researchers to identify its molecular mechanisms. The high expression of genes such as secreted frizzled-related protein 1 (sFRP1) might lead to activation of the signal pathway in the early stages of gastric cancer, promoting the process of tumor growth, proliferation, differentiation, and apoptosis3,4,5,6,7. sFRP1-overexpression cells showed an increase in the expression of TGF&#946;, its downstream targets, and TGF&#946;-mediated EMT8. Previous studies have demonstrated that the TGF-&#946;1 level is correlated with peritoneal metastasis and the TNM stages of gastric cancer. We have described the changes in cancer cell proliferation regulated by sFRP1 overexpression and TGF-&#946;1 inhibition, and established animal models for peritoneal metastasis to show the performance of tumor imaging under the effects of gene regulation.
Animal models for gastric cancer are indispensable tools for researching tumor development and experimenting with various therapeutic strategies without having to sacrifice animals. Animal models have proven useful in studying the formation mechanisms of tumors and cells of origin, determining the presence of cancer stem cells, and examining various novel therapeutic strategies. Therefore, a real-time non-invasive technique can provide an accurate description of the development of gastric tumors and tumor response to treatments, which can identify the development of peritoneal metastasis nodules in nude mice and monitor the changes of a tumor in response to various experimental and therapeutic interventions.
Currently, multi-detector CT (MDCT) plays an important role in the TNM staging of gastric cancers and is useful for predicting tumor resectability preoperatively9. However, radiological studies of patients with histologically proven gastric carcinoma have mainly been based on morphology. DECT imaging extends the parameters to reflect functional information by providing monochromatic images and may be helpful for improving the N staging accuracy for gastric cancers. Furthermore, this technique will enable the acquisition of material-decomposition images, which may be useful to differentiate between differentiated and undifferentiated gastric carcinoma, and between metastatic and non-metastatic lymph nodes10. With the introduction of DECT, the functional imaging aspect of CT has also been added to clinical applications, contributing to evaluations of therapeutic efficacy and predicting patient prognoses11,12,13. PET/CT is a useful imaging technique for the detection and staging of gastric cancer and can evaluate the recurrence of the tumor effectively14. Tumor cell proliferation and angiogenesis were both considered to be necessary in the development of a detectable tumor15, tumor nodules showed a positive performance with higher SUVmax on PET/CT. Based on their preference for aerobic glycolysis, 18F-FDG, a glucose analog, has been exploited as a promising tracer in the diagnosis of malignancies, combined with PET/CT16. This method relies on the rapid glucose consumption of tumor tissue and has broad clinical applications, including assisting in the detection, staging, and evaluation of the prognosis of tumors, as well as monitoring the tumors&#39; response to therapy17,18. As non-invasive methods, DECT and PET/CT have been utilized to diagnose malignant tumors and to assess tumor response to various therapies.
Our group has been using this non-invasive imaging method with DECT and PET/CT scanners to detect and monitor the process of tumor growth and metastasis in living mice19. We explored imaging findings induced by the sFRP1-overexpression in gastric cancer cells in vivo using nude mice, with DECT and PET/CT, and described the changes of the SUVmax value following targeted therapy by the TGF-&#946;1 inhibitor to confirm the development of tumor nodules in the peritoneum after gene induction, and also studied the changes in tumor nodules in response to experimental treatments. In this paper, we present detailed procedures for modeling gastric tumor peritoneal metastasis in mice, and its detection and monitoring with DECT and PET/CT.

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			<td height="21" style="height:21px;width:247px;">normal saline</td>
			<td style="width:389px;">HUNAN KELUN PHARMACEUTICAL CO,LTD</td>
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			<td height="21" style="height:21px;width:247px;">BALB/c nude mice&#160;</td>
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			<td height="30" style="height:31px;width:247px;">SGC-7901&#160; cells</td>
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			<td height="21" style="height:21px;width:247px;">AW Volumeshare5</td>
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			<td>dual-energy spectral CT workstation</td>
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			<td height="21" style="height:21px;width:247px;">Siemens Inveon micro-PET/CT</td>
			<td style="width:389px;">Siemens Preclinical Solution</td>
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			<td>positron emission tomography/ 
			computed tomography scanner&#160;</td>
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			<td height="21" style="height:21px;width:247px;">Inveon Acquisition Workplace</td>
			<td style="width:389px;">Siemens Preclinical Solution</td>
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			<td>PET-CT workstation</td>
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gene regulation and targeted therapy in gastric cancer peritoneal metastasis: radiological findings from dual energy ct and pet/ct

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 SUVmax (standardized uptake value) of nodules demonstrated an obvious alteration trend in response to targeted therapy of TGF-&#946;1 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.

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...

Watch this Scientific Journal Video about Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT at JoVE.com

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

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.

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 ...

The overall goal of this non-invasive imaging procedure is to connect research on gastric cancer peritoneal metastasis and the mechanisms of tumorigenesis and to monitor tumor growth and the effects of therapeutic interventions on gastric cancer. This method can help answer some key questions in a tumor research feud, such as how the peritoneal metastasis mechanism functions and how to perform early diagnosis, treatment, response monitoring and prognosis. The main advantage of this technique is that it can identify the region and the metastasis process of gastric cancer and it can monitor the kidneys in response to treatments.To begin this procedure establish the gastric cancer peritoneal metastasis animal model and set up the dual energy CT scan as outlined in the text protocol. After selecting and anesthetizing the experimental mice, click the new patient icon in the DECT program. Input the mouse's basic information including it's patient ID and name.Then in the user protocol section click abdomen protocol and select the animal DECT scan protocol to enter the operation interface. Move each anesthetized mouse onto an animal fixture platform in the supine position. Using tape fix the mouses tail to make sure it does not bend.Sterilize the tail with alcohol. After this move the CT scan bed so that the external positioning line laser is over the mouse's lower abdomen. When the positioning is complete click the reset button.Next click confirm. Follow the flashing order of the buttons on the keyboard to complete the scout scanning. Then select the next series icon and enter the interface for non-enhanced scanning.In the right screen set the start location and end location on the scout views to define the scan range. Maintain the same range in lateral scout and AP scout and cover the entire body volume of the animal. Click the confirm icon and then follow the flashing order of the buttons on the keyboard to complete the scout scanning.After this inject each mouse with iopamidol through the tail vein. Click next series to perform enhanced scanning. Set the start location and end location as before during the non-enhanced scan.Next click the confirm icon and follow the flashing order of the buttons on the keyboard to complete the dynamic enhanced scans, including arterial phase, portal phase and delayed phase. After this click end exam to exit the scanning interface. The image series will automatically be uploaded to the workstation.First locate the mice series on the DECT workstation interface. Select the plus C mono phase series list. Open the GSI volume viewer.And select the GSI VV general protocol from the GSI protocol manager interface. Then click the view type active annotation in the upper left corner of the image view ports and select coronal orientation from the drop down menu. Other orientation images like transverse or sagittal position can be selected from this drop-down menu as well.For one image view port click the volume one active annotation and select mono volumes from the drop-down menu. In a second image view port select iodine water volumes. Click and hold the left mouse button to drag the image from the iodine water view port to the mono view port.Check the mix the views box to get the color fused images. After this click and drag from the center of the image scroll icon to observe the images. Save any that show positive results as color fused images.To begin set up the micro pet CT imaging protocol as outlined in the text protocol. After injecting the FDG and anesthetizing move the animal to the entrance of the pet CT scanner. Click the laser icon from the toolbar viewer and use the touch pad control interface to move the bed so that the mouse's abdomen is located in the center of the pet and CT fields of view.In the laser aligned window select the first scan type as CT scan with pet acquisition included in the workflow as the option. Next open the scout view window and acquire a scout view XR radiograph. Adjust the position of the animal bed so that the CT center field of view is located at the center of the mouse's body.Select the prepared micro pet CT protocol. Input the number of mice to be successively imaged in the pop-up window. Click the set up option and enter the weight.Then click the set up option again and follow the pop up window instructions to complete the set up. Click the start workflow icon to start scanning. After the scanning is complete evaluate the quality of the acquired CT and pet images.Transfer the data through the network to the post imaging analysis. Next open the pet CT workstation software and import the CT and pet image series data. In the registration window click the general analysis option to register CT and pet images together.Then we click the button in the tools application to adjust the window and level of images. Under the review window choose the sky model to show a perfect alignment between the CT and pet images. In the region of interest quantification window identify the peritoneal nodules with references provided by the co-registered images.Draw the region of interest or ROI with tools over the fused images. Edit the size and shape of the ROI and record the maximum standard uptake value. Then output and save the selected merged images.In this study, DECT and pet CT scanning are performed on nude mice after two weeks of cell lined injections. GSI images yielded excellent results for displaying subcutaneous metastasis beyond the contour of the abdomen for the SFRP1 over expression group. And metastasis with peripheral enhancement is confirmed by color scale image.The acquired pet CT images depict focally abnormal FDG uptake of metastasis, including in the peritoneal and subcutaneous metastasis. The gross specimen and histological section further illustrate that peritoneal metastasis and large subcutaneous metastasis. The abdominal cavity in the SFRP1 empty loading group contains no visible lesions, obvious abnormal enhancements or high FDG uptake.However, the gross specimen and histological results confirm that implantation of this group was successful. Non-invasive imaging scans for mice treated with transforming growth factor beta one depict obvious enhancement and focal abnormal fludeoxyglucose uptake of metastasis. The gross specimens for this treatment group are seen to have only eight nodules of peritoneal metastasis with diffused distribution in the abdominal cavity.However, mice in the control group that was given normal saline also showed visible legions and focally abnormal uptake of metastasis. These gross specimens are seen to have 22 nodules of peritoneal metastasis and the local metastasis nodules were adherent to the abdominal cavity. We are attempting this procedure.It is important to make sure that the time period of each experiment or arrangement is reasonable. And performance study has the necessary animal For researchers in a feud of oncology and medicine to research the metastasis mechanism and prognosis evaluation for other tumors like ovarian cancer or rectal cancer. After watching this video you should with understanding of how to use a QCT in a part of CT to access the process of tumor peritoneal metastasis affected by and the treatment efficacy with Don't forget that working with imaging can be extremely hazardous and the precautions such as should always be taken while performing this procedure.

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