Systemic toxicity in mice induced by localized porphyrin photodynamic therapy.
An unexpected high level of acute lethality has been documented following Photofrin II-mediated photodynamic therapy (PDT) treatments which were localized to the hind leg of normal and tumor-bearing mice. Doses of PDT which induced lethality (10 mg/kg Photofrin II, 200-500 J/cm2) were in the range of doses required to obtain murine tumor cures. The percentage of lethality was proportional to the total light dose but was inversely proportional to the dose rate of delivered light. Comparable levels of acute toxicity were observed in four pigmented mouse strains (C57BL/6J, C3H/HeJ, DBA/1, and DBA/2) and in two albino mouse strains (BALB/c and Swiss Webster). Decreased sensitivity to PDT-induced lethality was observed in two pigmented mouse strains (B10D2/OSN and B10D2/NSN). The administration of warfarin, aspirin, indomethacin, or antihistamine had significant protective effects in terms of decreasing PDT-induced lethality. However, injection of cobra venom factor (to deplete C3 and C5 of the complement system) did not alter the lethality mediated by PDT. Histological profiles obtained 24 h following PDT demonstrated vascular congestion in the liver, kidney, lung, and spleen. Significant decreases in removable blood volume, core temperature, and spleen weight were also observed within 24 h of localized PDT treatment. These results indicate that PDT-induced lethality is consistent with a traumatic shock syndrome and suggest that endogenous vasoactive mediators of shock such as prostaglandins, thromboxanes, and histamine are associated with the lethality induced by localized PDT in mice.
Ferrario
A
A
Clayton Ocular Oncology Center, Childrens Hospital, Los Angeles, California 90027.
Gomer
C J
CJ
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D001772:Blood Cell Count; D017323:Dihematoporphyrin Ether; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006415:Hematoporphyrins / Q000633:toxicity*; D007213:Indomethacin / Q000627:therapeutic use; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D010778:Photochemotherapy / Q000009:adverse effects*; D012880:Skin Pigmentation; D014859:Warfarin / Q000627:therapeutic use
D006415:Hematoporphyrins; D014859:Warfarin; D017323:Dihematoporphyrin Ether; D001241:Aspirin; D007213:Indomethacin