Combined microPET/CT for imaging of hepatocellular carcinoma in mice

Christian von Falck^1,2, Thomas Rodt^1,2, Roman Halter², Reinhard Spanel³, Michael Galanski¹, Juergen Borlak²

1Institute of Radiology, Hannover Medical School, Hannover, Germany, ²Department of Pharmaceutical Research and Medical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, ³Institute of Pathology, Viersen, Germany

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Materials and methods

3.1. Tumor model and animal handling

3.2. In-vivo imaging

3.3. microCT imaging

3.4. microPET imaging

3.5. Image analysis and statistics

3.6. Necropsy and histopathology

3.7. Gene expression analysis

4. Results

4.1. In-vivo imaging: microCT

4.2. In-vivo imaging: microPET

4.3. Imaging of tumor growth

4.4. Expression of glucose transporters and hexokinases

4.5. Histopathology

5. Discussion

6. Acknowledgments

7. References

1. ABSTRACT

The EGF-transgenic mouse is a genetic model of hepatocellular carcinoma that allows for a comprehensive study of signal pathways, molecular interactions and the evaluation of novel therapeutic concepts. In this regard, non-invasive imaging tools for serial in-vivo monitoring of tumor load and growth are highly desirable. This study therefore aimed at demonstrating the feasibility of non-invasive in-vivo imaging of primary liver malignancies in mice using combined contrast-enhanced microCT and F-18 FDG microPET. In our murine disease model, microCT enabled imaging of primary liver tumors down to a lesional diameter of 0.9mm. F-18 FDG tumor-to-non-tumor ratio of HCCs was observed to be dependent on lesion size and linked to overpression of glucose transporters and hexokinase isoenzymes as determined by gene expression studies. Histopathologic analyses indicated an increased cellular dedifferentiation with increase lesion size, as well.