Experimental grounds for using chlorin e6 in the photodynamic therapy of malignant tumors.
The toxicity, pharmacokinetics and antitumour effect of chlorin e6 after light irradiation were studied. The LD50 value of chlorin e6 in C3H mice is 189 +/- 9 mg kg-1 and in Wistar white rats is 113 +/- 18 mg kg-1 14 days after intraperitoneal injection. The concentration of chlorin e6 in blood, liver, kidney, spleen and tumors (sarcoma M-1 and sarcoma 45) of the rats was determined by a fluorescence method, 3, 6, 12, 18, 24, 48 and 72 h after administration at a dose of 10 mg kg-1. For this purpose, chlorin e6 was extracted from tissues by the detergent Triton X-100. The depth of necrosis in sarcoma 45, the regression rate of sarcoma M-1 and the animal cure rate were evaluated after chlorin e6 administration at doses of 1-10 mg kg-1 and subsequent irradiation with krypton laser light. Depending on the dose and the time interval between chlorin e6 injection and irradiation, the depth of necrosis in sarcoma 45 varied from 5.0 to 15.0 mm. The cure rate of the animals with sarcoma M-1 varied from 10% to 60%. The antitumor effect was directly proportional to the chlorin e6 dose and light energy exposure and inversely proportional to the time interval between photosensitizer injection and irradiation.
Department of Chemoradiotherapy, Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
G A
GA
Kostenich
I N
IN
Zhuravkin
E A
EA
Zhavrid
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002735:Chlorophyllides; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008027:Light; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use* / Q000633:toxicity; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution
D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C062985:phytochlorin