Photodynamic therapy of oncogene-transformed cells.
Photodynamic therapy with dihematoporphyrin ether sensitizes malignant cells to damage by 630 nm light. The in vitro, in vivo photodynamic therapy sensitivity of a cell line transformed by the Kirsten ras oncogene (45342) was studied to establish a new photodynamic therapy model. With the colony formation assay, neither light alone nor dihematoporphyrin ether alone affected 45342 survival. Energy-dependent photodynamic therapy effects were seen in vitro in dihematoporphyrin ether-incubated and light-exposed cells (90% cytotoxicity = 950 joules/m2; 99% cytotoxicity = 1575 joules/m2; p2 less than 0.05). Subcutaneous allografts of 45342 were established in nu/nu mice, and ideal route (intravenous or intraperitoneal) of dihematoporphyrin ether delivery, dihematoporphyrin ether tissue kinetics, and in vivo photodynamic therapy effects were examined. Intravenous administration not only gave higher levels of the sensitizer in various tissues, but also was associated with less variation than the intraperitoneal route. Selective dihematoporphyrin ether retention was documented in the tumors at 24 hours after injection compared with other tissues, and photodynamic therapy with 0.3 W/cm2 to a total dose of 150 joules/cm2 led to progressive coagulative tumor necrosis and tumor regression. These studies confirm that transformed, malignant cells are sensitive to photodynamic therapy, and this model may prove in future studies to increase efficacy to photodynamic therapy (i.e., with dihematoporphyrin ether delivery by monoclonal antibodies).
Pass
H I
HI
Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Evans
S
S
Matthews
W A
WA
Perry
R
R
Venzon
D
D
Roth
J A
JA
Smith
P
P
D000818:Animals; D002461:Cell Line, Transformed / Q000187:drug effects; D017323:Dihematoporphyrin Ether; D006415:Hematoporphyrins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D008027:Light; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009857:Oncogenes; D010778:Photochemotherapy
D006415:Hematoporphyrins; D017323:Dihematoporphyrin Ether