Pharmacokinetic study of a gallium-porphyrin photo- and sono-sensitizer, ATX-70, in tumor-bearing mice.
The tissue distribution of a gallium-porphyrin photo- and sono-sensitizer, 7,12-bis(1-decyloxyethyl)-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 CDF(1) 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 concentrations 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.
Sasaki
K
K
Central Research Laboratory, Hitachi, Ltd., 1-280 Higashi-Koigakubu, Kokubunji, Tokyo 185-8601, Japan.
Yumita
N
N
Nishigaki
R
R
Sakata
I
I
Nakajima
S
S
Umemura
S I
SI
D000230:Adenocarcinoma / Q000097:blood / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000097:blood / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D005470:Fluorometry; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D017319:Photosensitizing Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011166:Porphyrins / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011485:Protein Binding; D014018:Tissue Distribution; D014464:Ultrasonic Therapy; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001798:Blood Proteins; D017319:Photosensitizing Agents; D011166:Porphyrins; C081908:ATX 70