Benzoporphyrin-lipoprotein-mediated photodestruction of intraocular tumors.
Benzoporphyrin derivative (BPD), a sensitizer currently in clinical trials, was evaluated for the treatment of experimental Greene melanoma implanted in the rabbit iris. To improve tumor targeting, BPD was complexed with low-density lipoprotein (LDL) representing an endogenous carrier system for BPD as previously described. Twelve tumors were irradiated at a sensitizer dose of 2 mg kg-1 body weight using a dye laser at 692 nm. Tumor responses were documented by photography, angiography and light and electron microscopy. All tumors treated with 80 J cm-2 regressed irreversibly. The principal mechanism of tumor necrosis was thrombosis following disruption of endothelial membranes. Ultrastructure data suggested tumor cell damage, although evidence for this being the result of direct PDT-mediated tumor cell death was less clear. These data suggest that BPD-LDL may be used to improve the selectivity of photodynamic tumor therapy possibly by the increased uptake of lipoprotein-delivered sensitizer to neovascular endothelial cells.
Schmidt-Erfurth
U
U
Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston USA.
Flotte
T J
TJ
Gragoudas
E S
ES
Schomacker
K
K
Birngruber
R
R
Hasan
T
T
D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers; D015811:Iris Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000648:ultrastructure; D008077:Lipoproteins, LDL; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D011166:Porphyrins / Q000627:therapeutic use*; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D004337:Drug Carriers; D008077:Lipoproteins, LDL; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C504224:benzoporphyrin D