title: Radiation pneumopathy in the rat after intravenous application of (188)Re-labeled microspheres.
abstract: OBJECTIVE
  To determine the dose dependence and kinetics of pneumopathy after systemic administration of rhenium-188 ((188)Re)-labeled microspheres in a rat model.
  
  
  METHODS
  (188)Re-microspheres were injected intravenously into adult Wistar rats (n = 54, age, 8 ± 2 months). The rats were divided into 6 groups according to the intended absorbed dose in the lung (maximum 60 Gy). Gamma camera scans were used to estimate the individual whole lung doses. One control group (n = 5) received nonlabeled microspheres. The breathing rate was measured before and weekly after the treatment using whole body plethysmography until 24 weeks. An increase in the breathing rate by 20% compared with the individual pretreatment control value was defined as the quantal endpoint for dose-effect analyses.
  
  
  RESULTS
  A biphasic increase in the breathing rate was observed. The first impairment of lung function occurred in Weeks 3-6. For late changes, the interval to onset was clearly dose dependent and was 17 weeks (10-30 Gy) and 10 weeks (50-60 Gy), respectively. The incidence of the response was highly dependent on the estimated lung dose. The median effective dose for an early and late response was virtually identical (19.9 ± 0.6 Gy and 20.4 ± 3.1 Gy, respectively). A significant correlation was found between the occurrence of an early and a late effect in the same rat, suggesting a strong consequential component.
  
  
  CONCLUSIONS
  The effects of radiolabeled microspheres can be studied longitudinally in a rat model, using changes in the breathing rate as the functional, clinically relevant response. The isoeffective doses from the present study using radionuclide administration and those from published investigations of homogeneous external beam radiotherapy are almost similar.
authors.affiliation: Department of Nuclear Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Liepe
authors.forename: Diana
authors.initials: D
authors.lastname: Faulhaber
authors.forename: Gerd
authors.initials: G
authors.lastname: Wunderlich
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Michael
authors.initials: M
authors.lastname: Haase
authors.forename: Roland
authors.initials: R
authors.lastname: Jung
authors.forename: Liane
authors.initials: L
authors.lastname: Oehme
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörr
authors.forename: Jörg
authors.initials: J
authors.lastname: Kotzerke
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D007275:Injections, Intravenous; D008102:Liver Circulation / Q000502:physiology; D008168:Lung / Q000503:physiopathology / Q000528:radiation effects*; D008297:Male; D008863:Microspheres; D011652:Pulmonary Circulation / Q000502:physiology; D017564:Radiation Pneumonitis / Q000503:physiopathology; D011868:Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D011878:Radiotherapy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D056152:Respiratory Rate / Q000528:radiation effects*; D012211:Rhenium / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D011868:Radioisotopes; D012211:Rhenium