Preliminary ¹⁹F-MRS Study of Tumor Cell Proliferation with 3'-deoxy-3'-fluorothymidine and Its Metabolite (FLT-MP)

The thymidine analogue 3'-deoxy-3'-[¹⁸F]fluorothymidine, or [¹⁸F]fluorothymidine ([¹⁸F]FLT), is used to measure tumor cell proliferation with positron emission tomography (PET) imaging technology in nuclear medicine. FLT is phosphorylated by thymidine kinase 1 (TK1) and then trapped inside cells; it is not incorporated into DNA. Imaging with ¹⁸F-radiolabeled FLT is a noninvasive technique to visualize cellular proliferation in tumors. However, it is difficult to distinguish between [¹⁸F]FLT and its metabolites by PET imaging, and quantification has not been attempted using current imaging methods. In this study, we successfully acquired in vivo¹⁹F spectra of natural or nonradioactive 3'-deoxy-3'-fluorothymidine ([¹⁹F]FLT) and its monophosphate metabolite (FLT-MP) in a tumor xenograft mouse model using 9.4T magnetic resonance imaging (MRI). This preliminary result demonstrates that ¹⁹F magnetic resonance spectroscopy (MRS) with FLT is suitable for the in vivo assessment of tumor aggressiveness and for early prediction of treatment response.