Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation

Nucl Med Biol. 2012 May;39(4):570-8. doi: 10.1016/j.nucmedbio.2011.10.012. Epub 2011 Dec 14.


Introduction: The translocator protein 18 kDa (TSPO), although minimally expressed in healthy brain, is up-regulated in pathological conditions, coinciding with microglial activation. It is thereby a suitable in vivo biomarker of neuroinflammation for detection, evaluation and therapeutic monitoring of brain diseases. We aimed to estimate the radiation dosimetry of the positron emission tomography (PET) TSPO radioligand [(18)F]DPA-714, and we evaluated in healthy volunteers its whole-body uptake and cerebral kinetics.

Methods: Biodistribution data from mice were used for the prediction of radiation dosimetry. In human studies, a 90-min dynamic PET scan was performed in seven healthy volunteers after injection of [(18)F]DPA-714 (245±45 MBq). Arterial and venous samples were collected from two subjects, and two additional subjects were submitted to whole-body acquisition. Regions of interest were defined over cerebral structures to obtain mean time-activity curves and to estimate the distribution volume ratios by Logan graphical analysis, and over peripheral organs to obtain standard uptake values.

Results: The effective dose estimated from biodistribution in mice was 17.2 μSv/MBq. Modeling of regional brain and plasma data showed good in vivo stability of [(18)F]DPA-714 in humans, with only 20% of blood metabolites 20 min postinjection (p.i.). Maximum cerebral uptake was observed 5 min p.i., followed by two decreasing phases: a rapid washout (5-30 min) followed by a slower phase for the remainder of PET acquisition. Whole-body images demonstrate high activity in the gallbladder, heart, spleen and kidneys.

Conclusions: This initial study in humans shows that [(18)F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable effective dose estimation. Therefore, [(18)F]DPA-714 could provide a sensitive measure of neuroinflammatory changes in subsequent clinical investigations.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Central Nervous System Diseases / diagnostic imaging
  • Central Nervous System Diseases / metabolism*
  • Female
  • Fluorine Radioisotopes*
  • Health*
  • Humans
  • Inflammation / diagnostic imaging
  • Inflammation / metabolism
  • Kinetics
  • Male
  • Mice
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Pyrazoles / metabolism
  • Pyrazoles / pharmacokinetics*
  • Pyrimidines / metabolism
  • Pyrimidines / pharmacokinetics*
  • Radiometry
  • Receptors, GABA / metabolism


  • Biomarkers
  • Fluorine Radioisotopes
  • N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
  • Pyrazoles
  • Pyrimidines
  • Receptors, GABA
  • TSPO protein, human