title: Antitumor effect of combination of hyperthermotherapy and 5-aminolevulinic acid (ALA).
abstract: BACKGROUND
  5-Aminolevulinic acid (ALA) is a precursor of heme. ALA is used as a photosensitive substance in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) because heme metabolism is abnormal in tumor cells and a photosensitive metabolite of heme synthesis from ALA, protoporphyrin IX (PpIX), specifically accumulates in tumors. We investigated the enhancement of the antitumor effect by combination of ALA and hyperthermotherapy (HT) using a transplanted tumor model with Lewis lung carcinoma cells (3LL) in mice.
  
  
  METHODS
  Animals were divided into four test groups: control (untreated), HT, and HT plus ALA (100 or 300 mg/kg) groups, and HT by bathing at 43°C for 20 min was performed at five days after transplantation. ALA was administered once at the above doses three hours before HT by intraperitoneal injection.
  
  
  RESULTS
  The tumor sizes at five days after HT were 5.2- and 2.6-times greater than those at the time of HT in the control and HT groups, respectively. In contrast, PpIX accumulation in the tumor region was noted three hours after ALA administration, the HT+ALA group given at 100 or 300 mg/kg of ALA inhibited tumor growth to 1.3- and 1.1-times increases in the tumor size.
  
  
  CONCLUSIONS
  Therefore, ALA administration markedly enhanced the tumor growth-inhibitory effect of HT.
authors.affiliation: SBI Pharmaceuticals Co., Ltd., 1-6-1-20F, Roppongi, Minato-ku Tokyo, 106-6020, Japan. kiwtakah@sbigroup.co.jp
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takeo
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishii
authors.forename: Atsuko
authors.initials: A
authors.lastname: Suzuki
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Kazuko
authors.initials: K
authors.lastname: Uno
authors.forename: Iuko
authors.initials: I
authors.lastname: Yasuda
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kishi
authors.forename: Kaori
authors.initials: K
authors.lastname: Sadamoto
authors.forename: Fuminori
authors.initials: F
authors.lastname: Abe
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006979:Hyperthermia, Induced; D008027:Light; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-Aminolevulinic acid; ALA; animal tumor model; hyperthermia; protoporphyrin IX