title: Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.
abstract: Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days).
authors.affiliation: Department of Neurosurgery, Osaka Medical College, Osaka, Japan, 569-8686.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawabata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Miyatake
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kuroiwa
authors.forename: Erhong
authors.initials: E
authors.lastname: Hao
authors.forename: M Graça H
authors.initials: MG
authors.lastname: Vicente
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D008297:Male; D008856:Microscopy, Fluorescence; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D001896:Boron Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C533262:tetrakis(4-carboranylthiotetrafluorophenyl)chlorin; D010649:Phenylalanine
keywords: BNCT; CED; CNS; PDT; TPFC; absorption; blood-brain barrier; boron-containing chlorin; cell culture; osmotic pumps