Evaluation of 5-[18F]fluoro-2'-deoxycytidine as a tumor imaging agent: A comparison of [18F]FdUrd, [18F]FLT and [18F]FDG

Abstract

One of the hallmarks of cancer is increased cell proliferation. Measurements of cell proliferation by estimation of DNA synthesis with several radiolabeled nucleosides have been tested to assess tumor growth. Deoxycytidine can be phosphorylated by deoxycytidine kinase (dCK) and is incorporated into DNA. This study evaluated a radiofluorinated deoxycytidine analog, 5-[¹⁸F]fluoro-2'-deoxycytidine ([¹⁸F]FdCyd), as a proliferation probe and compared it with 5-[¹⁸F]fluoro-2'-deoxyuridine ([¹⁸F]FdUrd), 3'-deoxy-3'-[¹⁸F]fluorothymidine ([¹⁸F]FLT), and [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) in a tumor-bearing mouse model. [¹⁸F]FdCyd was synthesized from two precursors by direct electrophilic substitution. The serum stability and partition coefficient of [¹⁸F]FdCyd were evaluated in vitro. Positron emission topography (PET) imaging of Lewis lung carcinoma (LLC)-bearing mice with [¹⁸F]FdCyd, [¹⁸F]FdUrd, [¹⁸F]FLT, and [¹⁸F]FDG were evaluated. [¹⁸F]FdCyd was stable in mouse serum and normal saline for up to 4 h. With all radiotracers except [¹⁸F]FLT, PET can clearly delineate the tumor lesion. [¹⁸F]FdCyd and [¹⁸F]FdUrd showed high accumulation in the liver and kidney. The SUV and tumor-to-muscle (T/M) ratios derived from PET imaging of the radiotracers were [¹⁸F]FDG > [¹⁸F]FdCyd > [¹⁸F]FdUrd > [¹⁸F]FLT. Selective retention in tumors with a favorable tumor/muscle ratio makes [¹⁸F]FdCyd a protential candidate for further investigation as a proliferation imaging agent.

Keywords: Nucleosides; PET; Proliferation; [(18)F]FLT; [(18)F]FdCyd.