Photodynamic therapy for experimental tumors using ATX-S10(Na), a hydrophilic chlorin photosensitizer, and diode laser.
ATX-S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second-generation photosensitizer for use in photodynamic therapy (PDT) for cancer treatment. The effectiveness of PDT using ATX-S10(Na) and a diode laser for experimental tumors was evaluated in vitro and in vivo. In-vitro PDT using ATX-S10(Na) and the diode laser showed drug concentration-, laser dose- and drug exposure time-dependent cytotoxicity to various human and mouse tumor cell lines. In Meth-A sarcoma-implanted mice, optimal PDT conditions were found where tumors were completely eliminated without any toxicity. Against human tumor xenografts in nude mice, the combined use of 5 mg / kg ATX-S10(Na) and 200 J / cm(2) laser irradiation 3 h after ATX-S10(Na) administration showed excellent anti-tumor activity, and its efficacy was almost the same as that of PDT using 20 mg / kg porfimer sodium and a 100 J / cm(2) excimer dye laser 48 h after porfimer sodium injection. Microscopic observation of tumor tissues revealed that PDT using ATX-S10(Na) and the diode laser induced congestion, thrombus and degeneration of endothelial cells in tumor vessels, indicating that a vascular shutdown effect plays an important role in the anti-tumor activity of PDT using ATX-S10(Na) and the diode laser.
Medical Research Laboratories, Wyeth Lederle Japan, Ltd., Kashiwa-cho, Shiki 353-8511, Japan. morim@labs.wyeth.com
M
M
Mori
I
I
Sakata
T
T
Hirano
A
A
Obana
S
S
Nakajima
M
M
Hikida
T
T
Kumagai
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D007834:Lasers; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000473:pathology; D014183:Transplantation, Heterologous
C115550:ATX-S10; D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D017323:Dihematoporphyrin Ether