Imaging of tumor hypoxia with [124I]IAZA in comparison with [18F]FMISO and [18F]FAZA--first small animal PET results

J Pharm Pharm Sci. 2007;10(2):203-11.


Purpose: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia*
  • Cell Line, Tumor
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Humans
  • Iodine Radioisotopes / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms / diagnostic imaging*
  • Neoplasms / metabolism
  • Nitroimidazoles* / pharmacokinetics
  • Positron-Emission Tomography
  • Radiopharmaceuticals* / pharmacokinetics
  • Tissue Distribution


  • Fluorine Radioisotopes
  • Iodine Radioisotopes
  • Nitroimidazoles
  • Radiopharmaceuticals