Pharmacokinetic study of a gallium-porphyrin photo- and sono-sensitizer, ATX-70, in tumor-bearing mice

Abstract

The tissue distribution of a gallium-porphyrin photo- and sono-sensitizer,7,12-bis(1-decyloxy-ethyl)-Ga(III)-3,8,13,17- tetramethylporphyrin-2,18-dipropionyldiaspartic acid, ATX-70, was pharmacokinetically examined in tumor-bearing mice. The drug was administered intravenously to CDF1 mice implanted with Colon 26 carcinoma. Blood and tissue samples were collected for up to 72 h after administration. The drug concentration was determined by high-performance liquid chromatography (HPLC) with fluorescence detection. ATX-70 was found to accumulate in tumors at a relatively high concentration that peaked between 2 h and 6 h after administration. However, modest concentration of ATX-70 also remained in healthy tissues for up to 6 h. We examined the distribution of ATX-70 in the tumor in comparison with other tissues from the viewpoint of minimizing possible side effects of laser or ultrasound exposure while maintaining the treatment effect. About 24 h after administration, the tumor/plasma concentration ratio peaked, and relatively high tumor/skin and tumor/muscle concentration ratios were seen.