Biodistribution and dosimetry of (18)F-EF5 in cancer patients with preliminary comparison of (18)F-EF5 uptake versus EF5 binding in human glioblastoma

Eur J Nucl Med Mol Imaging. 2010 Nov;37(11):2048-59. doi: 10.1007/s00259-010-1517-y. Epub 2010 Jun 29.


Purpose: The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of (18)F-EF5, a lipophilic 2-nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of (18)F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies.

Methods: (18)F-EF5 was synthesized by electrophilic addition of (18)F(2) gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0° then purified and administered by intravenous bolus. Three whole-body images were collected for each of ten patients using an Allegro (Philips) scanner. Gamma counts were determined in blood, drawn during each image, and urine, pooled as a single sample. PET images were analyzed to determine radiotracer uptake in several tissues and the resulting radiation dose calculated using OLINDA software and standard phantom. For three patients, 21 mg/kg unlabeled EF5 was administered after the PET scans, and tissue samples obtained the next day at surgery to determine EF5 binding using immunohistochemistry techniques (IHC).

Results: EF5 distributes evenly throughout soft tissue within minutes of injection. Its concentration in blood over the typical time frame of the study (∼3.5 h) was nearly constant, consistent with a previously determined EF5 plasma half-life of ∼13 h. Elimination was primarily via urine and bile. Radiation exposure from labeled EF5 is similar to other (18)F-labeled imaging agents (e.g., FDG and FMISO). In a de novo glioblastoma multiforme patient, focal uptake of (18)F-EF5 was confirmed by IHC.

Conclusion: These results confirm predictions of biodistribution and safety based on EF5's characteristics (high biological stability, high lipophilicity). EF5 is a novel hypoxia marker with unique pharmacological characteristics allowing both noninvasive and invasive measurements.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Transport
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Hypoxia
  • Etanidazole / analogs & derivatives*
  • Etanidazole / metabolism
  • Etanidazole / pharmacokinetics
  • Female
  • Fluorine Radioisotopes*
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Hydrocarbons, Fluorinated / metabolism*
  • Hydrocarbons, Fluorinated / pharmacokinetics*
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Radiometry
  • Tissue Distribution
  • Whole Body Imaging


  • Fluorine Radioisotopes
  • Hydrocarbons, Fluorinated
  • Etanidazole
  • 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide