Mechanism of tumor destruction following photodynamic therapy with hematoporphyrin derivative, chlorin, and phthalocyanine.
The effect of photodynamic therapy on the tumor microvasculature in the first few hours after treatment was studied at the light and electron microscopy levels. BALB/c mice with EMT-6 tumor received ip injections of hematoporphyrin derivative, chlorin, or phthalocyanine, and 24 hours later, the tumors were treated with light at 100 J/cm2 at the appropriate therapeutic wavelength for each photosensitizer. Animals were killed and their tumors removed at time 0, 30 minutes, 1 hour, and 2, 4, 6, 8, 12, 16, and 24 hours after treatment. The results indicate that for all three sensitizers the effects of photodynamic therapy leading to rapid necrosis of tumor tissue are not the result of direct tumor cell kill but are secondary to destruction of the tumor microvasculature. The first observable signs of destruction occur in the subendothelial zone of the tumor capillary wall. This zone, composed of dense collagen fibers and other connective tissue elements, is destroyed in the first few hours after phototherapy. However, the ultrastructural changes seen in this zone are different for the hematoporphyrin derivative, compared with chlorin and phthalocyanine. Binding of photosensitizers to the elements in this zone as well as altered permeability and transport through the endothelial cell layer because of the increased intraluminal pressure may be key features of tumor destruction.
Nelson
J S
JS
Beckman Laser Institute and Medical Clinic, Irvine, CA 92715.
Liaw
L H
LH
Orenstein
A
A
Roberts
W G
WG
Berns
M W
MW
D000818:Animals; D005260:Female; D017324:Hematoporphyrin Derivative; D006414:Hematoporphyrin Photoradiation; D006415:Hematoporphyrins / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure*; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000648:ultrastructure; D010778:Photochemotherapy; D011166:Porphyrins / Q000494:pharmacology*
D006415:Hematoporphyrins; D007211:Indoles; D054833:Isoindoles; D011166:Porphyrins; C006969:chlorin; D017324:Hematoporphyrin Derivative; C013647:phthalocyanine