Il Minn1, Amnon Bar-Shir1,2, Keerthi Yarlagadda1, Jeff W M Bulte1,2, Paul B Fisher3,4,5, Hao Wang6, Assaf A Gilad1,2, Martin G Pomper1,7. 1. The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 2. Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 3. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA. 4. VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia, USA. 5. VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA. 6. Division of Biostatistics and Bioinformatics, The Johns Hopkins University, Baltimore, Maryland, USA. 7. Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, Maryland, USA.
Abstract
PURPOSE: To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI. METHODS: Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9L(CMV-LRP) and 9L(PEG-LRP) , were established and tested for CEST contrast in vitro and in vivo. RESULTS: 9L(PEG-LRP) cells showed increased CEST contrast compared with 9L cells in vitro. Both 9L(CMV-LRP) and 9L(PEG-LRP) cells were capable of generating tumors in the brains of mice, with a similar growth rate to tumors derived from wild-type 9L cells. An increase in CEST contrast was clearly visible in tumors derived from both 9L(CMV-LRP) and 9L(PEG-LRP) cells at 3.4 ppm. CONCLUSION: The PEG-3 promoter:LRP system can be used as a cancer-specific, molecular-genetic imaging reporter system in vivo. Because of the ubiquity of MR imaging in clinical practice, sensors of this class can be used to translate molecular-genetic imaging rapidly.
PURPOSE: To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI. METHODS: Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9Lglioma, 9L(CMV-LRP) and 9L(PEG-LRP) , were established and tested for CEST contrast in vitro and in vivo. RESULTS: 9L(PEG-LRP) cells showed increased CEST contrast compared with 9L cells in vitro. Both 9L(CMV-LRP) and 9L(PEG-LRP) cells were capable of generating tumors in the brains of mice, with a similar growth rate to tumors derived from wild-type 9L cells. An increase in CEST contrast was clearly visible in tumors derived from both 9L(CMV-LRP) and 9L(PEG-LRP) cells at 3.4 ppm. CONCLUSION: The PEG-3 promoter:LRP system can be used as a cancer-specific, molecular-genetic imaging reporter system in vivo. Because of the ubiquity of MR imaging in clinical practice, sensors of this class can be used to translate molecular-genetic imaging rapidly.
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