Abstract #1722

Design of Thymidine Analogs as CEST Reporters for Imaging of HSV1-TK Expression

Amnon Bar-Shir^1,2, Guanshu Liu^1,3, Michael T. McMahon^1,3, Martin G. Pomper⁴, Peter C. van Zijl^1,3, Jeff W. Bulte^1,2, Assaf A. Gilad^1,2

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.