Photodynamic therapy of experimental choroidal melanoma using lipoprotein-delivered benzoporphyrin.
BACKGROUND
Benzoporphyrin derivative monoacid (BPD) is a new photosensitizer currently undergoing clinical trial for cutaneous malignancies. Compared with the clinically most frequently used sensitizer, Photofrin, BPD may offer higher tumor phototoxicity, better tissue penetration, and absence of significant skin sensitization. Low-density lipoprotein (LDL) carriers heighten efficiency and selectivity of BPD because neovascular and tumor cells express an increased number of LDL receptors. Hence, in addition to the vaso-occlusive effects similar to most other photosensitizers, LDL-BPD also has been shown to cause direct tumor cell damage.


METHODS
Benzoporphyrin derivative monoacid was complexed with human LDL and used in photodynamic treatment of choroidal melanomas experimentally induced in eight albino rabbits. Five rabbits served as controls. Three hours after intravenous injection of 2 mg/kg body weight of LDL-BPD, eight tumors were irradiated at 692 nm and 100 J/cm2 via an argon-pumped dye laser coupled into a slit lamp.


RESULTS
Angiography and histologic findings showed immediate photothrombosis after disintegration of endothelial membranes. After complete necrosis of tumor cells within 24 hours, a small fibrotic scar slowly developed. No tumor regrowth was noted up to 6 weeks when animals were killed.


CONCLUSIONS
These data suggest that photodynamic treatment with LDL-BPD may be a promising modality for multiple clinical applications, including tumors and neovascularizations II.
Schmidt-Erfurth
U
U
Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Bauman
W
W
Gragoudas
E
E
Flotte
T J
TJ
Michaud
N A
NA
Birngruber
R
R
Hasan
T
T
D000818:Animals; D002830:Choroid Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers; D005654:Fundus Oculi; D007275:Injections, Intravenous; D053685:Laser Therapy; D008077:Lipoproteins, LDL; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009374:Neoplasms, Experimental; D010778:Photochemotherapy; D011166:Porphyrins / Q000008:administration & dosage* / Q000009:adverse effects; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects
D004337:Drug Carriers; D008077:Lipoproteins, LDL; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C504224:benzoporphyrin D