Amnon Bar-Shir1,2, Guanshu Liu1,3,
Michael T. McMahon1,3, Martin G. Pomper4, Peter C. van
Zijl1,3, Jeff W. Bulte1,2, Assaf A. Gilad1,2
1Division of MR Research,
The Russel H. Morgan Department of Radiology, The Johns Hopkins University
School of Medicine, Baltimore, MD, United States; 2Cellular
Imaging Section, Institute for Cell Engineering, The Johns Hopkins University
School of Medicine, Baltimore, MD, United States; 3F.M. Kirby
Research Center for Functional Brain Imaging, Kennedy Krieger Institute,
Baltimore, MD, United States; 4The Russel H. Morgan Department of
Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD,
United States
Herpes simplex virus type-1 thymidine kinase (HSV1-TK) is an enzyme that phosphorylates a wide range of nucleoside analogs and has been used extensively for imaging gene expression using positron emission tomography (PET). Here we demonstrate for the first time that native nucleosides can generate specific MRI contrast based on the chemical exchange saturation transfer (CEST) mechanism. Furthermore, chemical modifications can improve their CEST-MRI fingerprints considerably. Specifically, the synthetic analog 5,6-dihydrothymidine (DHT) and thymidine triphosphate improved, by more than two-fold, the CEST-MRI contrast over thymidine. These results indicate that using these substrates, HSV1-TK can be used as CEST-MRI reporter.