Abstract
1936
Objectives As previously reported, the sugar-modified nucleosides have to be phosphorylated by cellular or viral enzymes in order to exert their biological activity. For that reason, we tried to develop D-arabinohexitol derivative (ADIDA) as potential HSV-TK imaging agent.
Methods ADIDA precursor was synthesized in 5 steps from glucose1-3. Radioactive ADIDA was prepared by iodine labeling method and hydrolysis. It was purified by HPLC using a C-18 column with 5% EtOH/H2O. For cytotoxicity analysis, MCA rat hepatoma cells and MCA-TK (HSV1-TK positive) cells were treated with various concentration of FIAU, ADIDA and GCV. Tumors were implanted using MCA on the left flank and MCA-tk on the right one. Planar images were acquired with a γ-camera at 1 h, 4 h after [131I] ADIDA injection.
Results In particular, we used C-18 Sep-Pak cartridge to remove impurities before deprotection. Purified radio compound was compared with pure standard using HPLC. Furthermore, FIAU (IC50, 1.11 x 10-7 M) and GCV (IC50, 1.17 x 10-7 M) of cyotoxicity measurement were shown to be more toxic than ADIDA (IC50, 1.85 x 10-5 M) in MCA-TK cells. However, γ-camera image of ADIDA did not show significant difference between MCA and MCA-tk tumor bearing mice model.
Conclusions We successfully prepared the high purity radioactive ADIDA, and also showed the possibility for HSV-TK imaging agent development.
- © 2009 by Society of Nuclear Medicine