Selective accumulation and strong photodynamic effects of a new photosensitizer, ATX-S10.Na (II), in experimental malignant glioma.
We investigated the feasibility of a novel photosensitizer, ATX-S10.Na (II), in photodynamic therapy (PDT) for glioma. First, PDT was performed in various brain tumor cell lines in vitro. Cytotoxicity depended upon both drug concentration and laser energy and the 50% inhibitory concentration ranged from 3.5 to 20 microg/ml. Next, PDT was performed in the subcutaneous and intracranial 9L tumor models in Fischer rats using ATX-S10.Na (II) and light from a 670-nm diode laser delivered by intratumoral insertion of an optical fiber. The effect of PDT on brain tumors was evaluated using magnetic resonance imaging. Sequential changes of the ATX-S10.Na (II) concentrations were also measured quantitatively by fluorospectrometry up to 12 h after intravenous administration in rats with intracranial and subcutaneous tumors. The concentration of ATX-S10.Na (II) in the brain tumor reached a maximum at 2 h after administration and the tumor/normal brain concentration ratio was as high as 131 at 8 h. Intratumoral PDT for intracranial tumors irradiated at this timing showed an obvious anti-tumor effect without severe side effects. The present study demonstrated the highly selective accumulation of ATX-S10.Na (II) in tumor tissue and its potent photodynamic effect in an experimental malignant glioma model.
Yamamoto
Junkoh
J
Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
Hirano
Toru
T
Li
Shaoyi
S
Koide
Masayo
M
Kohno
Eiji
E
Inenaga
Chikanori
C
Tokuyama
Tsutomu
T
Yokota
Naoki
N
Yamamoto
Seiji
S
Terakawa
Susumu
S
Namba
Hiroki
H
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology* / Q000662:veterinary; D005910:Glioma / Q000473:pathology* / Q000662:veterinary; D008279:Magnetic Resonance Imaging / Q000662:veterinary; D011166:Porphyrins / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
C117772:ATX S10Na(II); D011166:Porphyrins