title: Uptake of 18F-fluorocholine, 18F-fluoroethyl-L-tyrosine, and 18F-FDG in acute cerebral radiation injury in the rat: implications for separation of radiation necrosis from tumor recurrence.
abstract: Differentiation between posttherapy radiation necrosis and recurrent tumor in humans with brain tumor is still a difficult diagnostic task. The new PET tracers (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluorocholine (N,N-dimethyl-N-(18)F-fluoromethyl-2-hydroxyethylammonium [FCH]) have shown promise for improving diagnostic accuracy. This study assessed uptake of these tracers in experimental radiation injury.
  
  
  METHODS
  In a first model, circumscribed lesions were induced in the cortex of 35 rats using proton irradiation of 150 or 250 Gy. After radiation injury developed, uptake of (18)F-FET, (18)F-FCH, and (18)F-FDG was measured using autoradiography and correlated with histology and disruption of the blood-brain barrier as determined with Evans blue. In a second model, uptake of the tracers was assessed in acute cryolesions, which are characterized by the absence of inflammatory cells.
  
  
  RESULTS
  Mean (18)F-FET, (18)F-FCH, and (18)F-FDG standardized uptake values in the most active part of the radiation lesion and the contralateral normal cortex (in parentheses) were 2.27 +/- 0.46 (1.42 +/- 0.23), 2.52 +/- 0.42 (0.61 +/- 0.12), and 6.21 +/- 1.19 (4.35 +/- 0.47). The degree of uptake of (18)F-FCH and (18)F-FDG correlated with the density of macrophages. In cryolesions, (18)F-FET uptake was similar to that in radiation lesions, and (18)F-FCH uptake was significantly reduced.
  
  
  CONCLUSIONS
  Comparison of tracer accumulation in cryolesions and radiation injuries demonstrates that (18)F-FET uptake is most likely due to a disruption of the blood-brain barrier alone, whereas (18)F-FCH is additionally trapped by macrophages. Uptake of both tracers in the radiation injuries is generally lower than the published uptake in tumors, suggesting that (18)F-FET and (18)F-FCH are promising tracers for separating radiation necrosis from tumor recurrence. However, the comparability of our data with the literature is limited by factors such as different species and acquisition protocols and modalities. Thus, more studies are needed to settle this issue. Nevertheless, (18)F-FCH and (18)F-FET seem superior to (18)F-FDG for this purpose.
authors.affiliation: PET Center, Division of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Spaeth
authors.forename: Matthias T
authors.initials: MT
authors.lastname: Wyss
authors.forename: Bruno
authors.initials: B
authors.lastname: Weber
authors.forename: Stephan
authors.initials: S
authors.lastname: Scheidegger
authors.forename: Amelie
authors.initials: A
authors.lastname: Lutz
authors.forename: Jorn
authors.initials: J
authors.lastname: Verwey
authors.forename: Ivan
authors.initials: I
authors.lastname: Radovanovic
authors.forename: Jens
authors.initials: J
authors.lastname: Pahnke
authors.forename: Damian
authors.initials: D
authors.lastname: Wild
authors.forename: Gerrit
authors.initials: G
authors.lastname: Westera
authors.forename: Dominik
authors.initials: D
authors.lastname: Weishaupt
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Hermann
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaser-Hotz
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000378:metabolism*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D008297:Male; D009336:Necrosis; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics*; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
chemical_list: D005462:Fluorine Radioisotopes; C117289:O-(2-fluoroethyl)tyrosine; D000644:Quaternary Ammonium Compounds; D019275:Radiopharmaceuticals; C419185:fluoromethyl dimethyl-2-hydroxyethylammonium; D019788:Fluorodeoxyglucose F18; D014443:Tyrosine