title: High-dose-rate brachytherapy: dose escalation in three-dimensional miniorgans of the human bronchial wall.
abstract: OBJECTIVE
  High-dose-rate (HDR) brachytherapy of human lung cancer is well established, however fractionation schemes and dosages are based mainly on experience. The aim of this investigation was to study the effects of different doses of HDR iridium-192 on normal human bronchial epithelium in three-dimensional miniorgans of the human bronchial wall.
  
  
  METHODS
  Forty-eight biopsies from normal bronchi were cultivated for 14 days and exposed at random to different doses of HDR iridium 192 (0 Gy, 30 Gy, 45 Gy, 60 Gy, or 75 Gy). Cell viability was assessed immediately after irradiation, after 4 or 18 days by fluorescent staining, and cell damage of the culture was analyzed by light microscopy. Lactate dehydrogenase (LDH) was measured in the supernatant for 4 days.
  
  
  RESULTS
  There was no histologically apparent tissue damage regardless of the irradiation dose. The number of nonvital cells increased in irradiated miniorgans depending on the dose used (p < 0. 05 at 75 Gy). This effect occurred early and was less pronounced with time. LDH measurements showed an increase only in the first 24 hours.
  
  
  CONCLUSIONS
  Our results confirm that normal bronchial epithelium has a high tolerance to early epithelial damage by irradiation. This model of human bronchial miniorgans is useful for further studies of the effects of irradiation on human bronchi.
authors.affiliation: Department of Radiology, Klinikum Innenstadt, University of Munich, Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Kotsianos
authors.forename: D
authors.initials: D
authors.lastname: Bach
authors.forename: F
authors.initials: F
authors.lastname: Gamarra
authors.forename: W
authors.initials: W
authors.lastname: Haimerl
authors.forename: R
authors.initials: R
authors.lastname: Knüchel
authors.forename: S M
authors.initials: SM
authors.lastname: Lang
authors.forename: K J
authors.initials: KJ
authors.lastname: Pfeifer
authors.forename: R M
authors.initials: RM
authors.lastname: Huber
mesh_terms: D001918:Brachytherapy; D001980:Bronchi / Q000528:radiation effects*; D002470:Cell Survival; D006801:Humans; D007496:Iridium Radioisotopes; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009924:Organ Culture Techniques / Q000379:methods*; D011829:Radiation Dosage; D011853:Radiobiology; D020545:Respiratory Mucosa / Q000528:radiation effects*
chemical_list: D007496:Iridium Radioisotopes; D007770:L-Lactate Dehydrogenase