Talaporfin-mediated photodynamic therapy for peritoneal metastasis of gastric cancer in an in vivo mouse model: drug distribution and efficacy studies.
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.
Kishi
Kentaro
K
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinariku, Osaka, Osaka 537-8511, Japan. kisi-ke@mc.pref.osaka.jp
Yano
Masahiko
M
Inoue
Masahiro
M
Miyashiro
Isao
I
Motoori
Masaaki
M
Tanaka
Koji
K
Goto
Kunihito
K
Eguchi
Hidetoshi
H
Noura
Shingo
S
Yamada
Terumasa
T
Ohue
Masayuki
M
Ohigashi
Hiroaki
H
Ishikawa
Osamu
O
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
D017319:Photosensitizing Agents; D011166:Porphyrins; C053434:Talaporfin