Synthesis and biological evaluation of [124,125I]-FIAC for a new imaging of HSV1-TK gene expression

Objectives Modified the base part of nucleosides has led to the development of some nucleoside analogues with antiviral properties. All modified compounds have on common that they have to be phosphorylated by cellular or viral enzymes in order to exert their biological activity. A series of nucleoside analogues from which, until now, no congener has been attributed with significant antiviral activity are those containing a 5-iodocytosine base moiety.

Methods To synthesis of authentic compound, FIAC, was prepared in several steps from a commercially available β-D-Ribofuranose 1-acetate 2,3,5-tribenzoate. Radioiodine labeled FIAC was synthesis by two steps such as labeling and hydrolysis as shown in scheme. Radioiodine labeling used general iodine labeling method and the hydrolysis step was added sodium methoxide.

Results The product was purified using reverse-phase HPLC with an appropriate solvent (10/90/0.1% ACN/H2O/TFA) at a flow rate of 1 mL/min. The radiochemical purity of the product was >99% with decay-corrected yields of 50-65%. Purified radioactive compound was confirmed using co-injection with pure standard analogue. In vitro uptake study was performed in HSV1-TK expressing MCA-TK+ cells and MCA cells to compare the accumulation of [125I] FIAC. [125I] FIAC was evaluated by cellular uptake test in MCA and MCA-TK cell lines. Accumulation of [125I] FIAC in MCA-TK cells followed the result that continuously increased upto 8h.

Conclusions The result of this uptake study showed several folder higher selectively in MCA-TK+ cells than MCA cells after 8h. This study will be usefully application for micro imaging of MCA-TK+ and MCA cells.

Research Support This work was supported by the Seoul Research and Business Development Program (grant number 10574)