Effects of photodynamic therapy using mono-L-aspartyl chlorin e6 on vessels and its contribution to the antitumor effect.
The effect of photodynamic therapy (PDT) on the vascular system has a significant role in tumor tissue destruction. We investigated the contribution of vascular damage to the antitumor effects of PDT and analyzed the quantitative vascular changes after PDT. Fibrosarcoma-bearing BALB / c male mice were injected with mono-L-aspartyl chlorin e6 (NPe6) at a dose of 0.25, 5 or 15 mg / kg, and photoradiation was performed with a diode laser 10 min, 2 h or 24 h after injection, respectively. Ten minutes after injection of 0. 25 mg / kg, NPe6 was found to be present only in plasma, while at 2 h after injection of 5 mg / kg it was present in both plasma and tumor, and 24 h after injection of 15 mg / kg it was present only in the tumor. The antitumor effects observed in the 5 mg / kg-2 h and 0. 25 mg / kg-10 min groups were virtually the same, whereas the effect in the 15 mg / kg-24 h group was weaker. The damage to the tumor vasculature and tumor cells in the 15 mg / kg-24 h group occurred later than under the other conditions, and vascular damage in the tumor-surrounding tissue was also less marked even 24 h after PDT. These results suggested that the plasma NPe6 concentration during laser irradiation contributed more than the tumor NPe6 concentration to the antitumor effect, and that the minimal damage to blood vessels around the tumor at the low plasma NPe6 concentration may be one reason for the failure to obtain a marked antitumor effect.
Saito
K
K
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. koichi_saito@meiji. co.jp.
Mikuniya
N
N
Aizawa
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects; D005354:Fibrosarcoma / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D011166:Porphyrins / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; C053434:Talaporfin