title: Selective accumulation and strong photodynamic effects of a new photosensitizer, ATX-S10.Na (II), in experimental malignant glioma.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Junkoh
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Hirano
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Li
authors.forename: Masayo
authors.initials: M
authors.lastname: Koide
authors.forename: Eiji
authors.initials: E
authors.lastname: Kohno
authors.forename: Chikanori
authors.initials: C
authors.lastname: Inenaga
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tokuyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Yokota
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Terakawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Namba
mesh_terms: 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
chemical_list: C117772:ATX S10Na(II); D011166:Porphyrins