title: Talaporfin-mediated photodynamic therapy for peritoneal metastasis of gastric cancer in an in vivo mouse model: drug distribution and efficacy studies.
abstract: Photodynamic therapy (PDT) is a potential treatment for the peritoneal dissemination of gastric cancer, because its cytotoxicity is limited to superficial lesions. We examined the accumulation of talaporfin in peritoneal metastatic nodules and determined the optimal laser condition for these nodules. We also evaluated the pathological response after therapy. We created a peritoneal metastasis model in nude mice using the MKN-45 EGFP cell line. We evaluated the accumulation of talaporfin in peritoneal metastatic nodules and normal organs by spectrophotometric analysis 2-8 h after i.p. talaporfin. To determine optimal PDT conditions, we treated metastatic nodules and the small intestine using multiple laser doses (2, 5, and 10 J/cm2, respectively). Accumulation of talaporfin was detected in metastatic nodules in higher intensities than in the small intestine. The fluorescent intensity of the peritoneal metastatic nodules gradually decreased dependent on the time interval between the laser treatment and talaporfin administration. Fluorescent intensity in the small intestine decreased more than in the metastatic nodules. The pathological response rates by dose were 52.5% at 2 J/cm2, 43.2% at 5 J/cm2, and 64.4% at 10 J/cm2, respectively, when the laser treatment was used 2 h after talaporfin administration, whereas at 4 h, they were 20.8, 25.5, and 26.2%, respectively. Finally, the recommended treatment conditions were considered to be a 2 J/cm2 laser dose and a 4-h interval in terms of toxicity. Talaporfin-mediated PDT may be an effective treatment modality for patients with advanced gastric adenocarcinoma and metastatic peritoneal nodules.
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinariku, Osaka, Osaka 537-8511, Japan. kisi-ke@mc.pref.osaka.jp
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kishi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Isao
authors.initials: I
authors.lastname: Miyashiro
authors.forename: Masaaki
authors.initials: M
authors.lastname: Motoori
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kunihito
authors.initials: K
authors.lastname: Goto
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Shingo
authors.initials: S
authors.lastname: Noura
authors.forename: Terumasa
authors.initials: T
authors.lastname: Yamada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohue
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohigashi
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000556:secondary; D014018:Tissue Distribution
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C053434:Talaporfin