[Intraarterial infusion of hypoxic radiosensitizer RK28 in rabbit VX2 tumor system].
The effect of regional intra-arterial infusion of a hypoxic cell radiosensitizer RK28 (2-nitro-imidazole nucleoside analogue) on rabbit VX2 tumor was evaluated. Rabbits each weighing 2.5-3 kg were implanted with VX2 tumor in the left hind legs. Solid tumors grown up to 3 cm in diameter were treated with X-ray irradiation. Tumor volumes were assayed weekly by computed tomography (CT). Six rabbits were treated with 15 Gy of X-ray irradiation alone, and the other six rabbits were treated with intra-arterial infusion of RK28 (80 mg/kg) two minutes before 15 Gy of irradiation. The latter tumors regressed more rapidly than the former (p less than 0.01), and the latter rabbits seemed to survive longer than the former. The pharmacokinetics of RK28 and its metabolites in tumor tissue and serum were measured by high performance liquid chromatography (HPLC) using six rabbits. During irradiation, a high concentration of the agent was achieved in tumor tissue. It is suggested that a successful radiosensitizing effect will be obtained when regional intra-arterial infusion of RK28 is clinically combined with intraoperative radiation therapy and brachytherapy.
Suda
H
H
Department of Radiology, Yamaguchi University School of Medicine.
D000818:Animals; D015687:Cell Hypoxia; D003131:Combined Modality Therapy; D007261:Infusions, Intra-Arterial; D008297:Male; D008920:Misonidazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D011838:Radiation-Sensitizing Agents; C047778:1-(4'-hydroxy-2'-butenoxy)methyl-2-nitroimidazole; D008920:Misonidazole