Synthesis and evaluation of cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[(124)I]iodouracil: a new potential PET imaging agent for HSV1-tk expression

In our pursuit to find an appropriate reporter probe for herpes simplex virus type-1 thymidine kinase (HSV1-tk), a carbocyclic nucleoside analogue, cis-1-4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-124I]iodouracil, has been efficiently synthesized. A Pd(0)-catalyzed coupling reaction together with organotin and exchange reactions for radiolabeling gave more than 80% radiochemical yield with greater than 95% radiochemical purity and 1.15 GBq/mumol specific activity. Biological data reveal that the analogue is stable in vitro, less toxic than ganciclovir (GCV), and selective to HSV1-tk-expressed cells based on micro positron emission tomography (microPET) image analyses. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5-iodouridine (carbocyclic d4IU) is a potential imaging probe for HSV1-tk.