Tumor-specific expression and detection of a CEST reporter gene.
OBJECTIVE
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.


CONCLUSIONS
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.
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Il
I
Minn
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Amnon
A
Bar-Shir
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Keerthi
K
Yarlagadda
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jeff W M
JW
Bulte
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.|VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.|VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
Paul B
PB
Fisher
Division of Biostatistics and Bioinformatics, The Johns Hopkins University, Baltimore, Maryland, USA.
Hao
H
Wang
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Assaf A
AA
Gilad
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, Maryland, USA.
Martin G
MG
Pomper
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D017930:Genes, Reporter / Q000235:genetics*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor
PEG-3 promoter; chemical exchange saturation transfer; glioma; magnetic resonance imaging; molecular imaging