From PET to MRI: In vivo Mapping the HSV1-TK Reporter Gene with “hot-spot” 2H-MRI Using Synthetic Deuterated Thymidine Analog

Motivation: In the era of gene transfer, there is a need for non-invasive quantitative mapping of genetically engineered reporters that are applicable for clinically-translatable imaging modalities. Goal(s): To develop a quantitative 2H-MRI-based approach to map the expression of the HSV1-TK reporter gene, which is widely used for PET. Approach: A highly deuterated synthetic analog of thymidine (d6-5MDHT) was synthesized and proposed as a 2H-MRI reporter probe for mapping the expression of the HSV1-TK reporter gene. Results: We showed the ability to quantitatively map, in vivo, with 2H-MRI, the HSV1-TK_7B expression upon the accumulation of the administered d6-5MDHT only in tissues expressing the transgene. Impact: The successful implementation of the proposed 2H-MRI reporter system will allow the longitudinal quantitative mapping of a reporter gene expression, elucidating the kinetics and efficiency of gene and cell therapies employed in basic research and the clinic.