title: Imaging of tumor hypoxia with [124I]IAZA in comparison with [18F]FMISO and [18F]FAZA--first small animal PET results.
abstract: OBJECTIVE
  This study was performed to compare the 2-nitroimidazole derivatives [124I]IAZA, [18F]FAZA and well known [18F]FMISO in visualization of tumor hypoxia in a mouse model of human cancer using small animal PET.
  
  
  METHODS
  PET imaging of female Balb/c nude mice bearing A431 tumors on a Phillips Mosaic small animal PET scanner was performed 3 h p.i. for all three tracers. Mice injected with [124I]IAZA were scanned again after 24 h and 48 h. In addition to the mice breathing air, in the case of [18F]FAZA and [124I]IAZA a second group of mice for each tracer was kept in an atmosphere of carbogen gas (5% of CO2 + 95 % of O2; from 1 h before to 3 h after injection) to evaluate the oxygenation dependency on uptake (all experiments n = 4). After the final PET scan animals were sacrificed and biodistribution was studied.
  
  
  RESULTS
  Mice injected with [18F]FAZA displayed significantly higher tumor-to background (T/B) ratios (5.19 +/- 0.73) compared to those injected with [18F]FMISO (3.98 +/- 0.66; P $lt; 0.05) or [124I]IAZA (2.06 +/- 0.26; P $lt; 0.001) 3 h p.i. Carbogen breathing mice showed lower ratios ([18F]FAZA: 4.06 +/- 0.59; [124I]IAZA: 2.02 +/- 0.36). The T/B ratios increased for [124I]IAZA with time (24 h: 3.83 +/- 0.61; 48 h: 4.20 +/- 0.80), but after these late time points the absolute whole body activity was very low, as could be seen from the biodistribution data (< 0.1 %ID/g for each investigated organ) and ratios were still lower than for [18F]FAZA 3 h p.i. Due to de-iodination uptake in thyroid was high. Biodistribution data were in good agreement with the PET results.
  
  
  CONCLUSIONS
  [18F]FAZA showed superior biokinetics compared to [18F]FMISO and [124I]IAZA in this study. Imaging at later time points that are not possible with the short lived 18F labeled tracers resulted in no advantage for [124I]IAZA, i. e. tumor to normal tissue ratios could not be improved.
authors: Radiopharmacy, PET-Center, University of Tubingen, Tubingen, Germany. gerald.reischl@uni-tuebingen.de <reischl@uni-tuebingen.de>
authors: Gerald
authors: G
authors: Reischl
authors: Donna S
authors: DS
authors: Dorow
authors: Carleen
authors: C
authors: Cullinane
authors: Andrew
authors: A
authors: Katsifis
authors: Peter
authors: P
authors: Roselt
authors: David
authors: D
authors: Binns
authors: Rodney J
authors: RJ
authors: Hicks
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals