[11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: a comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis

Mol Imaging Biol. Nov-Dec 2009;11(6):386-98. doi: 10.1007/s11307-009-0211-6. Epub 2009 Mar 28.

Abstract

Background: Activation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [(11)C]-(R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [(11)C]-(R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [(11)C]-DPA-713 and [(18)F]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis.

Materials and methods: Rats were intranasally inoculated with HSV-1. On day 6 or 7 after inoculation, small animal PET studies were performed to compare [(11)C]-(R)-PK11195, [(11)C]-DPA-713, and [(18)F]-DPA-714.

Results: Uptake of [(11)C]-DPA-713 in infected brain areas was comparable to that of [(11)C]-(R)-PK11195, but [(11)C]-DPA-713 showed lower non-specific binding. Non-specific uptake of [(18)F]-DPA-714 was lower than that of [(11)C]-(R)-PK11195. In the infected brain, total [(18)F]-DPA-714 uptake was lower than that of [(11)C]-(R)-PK11195, with comparable specific uptake.

Conclusions: [(11)C]-DPA-713 may be more suitable for visualizing mild inflammation than [(11)C]-(R)-PK11195. In addition, the fact that [(18)F]-DPA-714 is an agonist PET tracer opens new possibilities to evaluate different aspects of neuroinflammation. Therefore, both tracers warrant further investigation in animal models and in a clinical setting.

Publication types

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

MeSH terms

  • Acetamides / chemistry
  • Acetamides / metabolism*
  • Animals
  • Animals, Outbred Strains
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Carbon Radioisotopes / metabolism
  • Carrier Proteins / metabolism*
  • Disease Models, Animal
  • Encephalitis, Herpes Simplex / diagnostic imaging*
  • Encephalitis, Herpes Simplex / metabolism
  • Fluorine Radioisotopes / metabolism
  • Immunohistochemistry
  • Isoquinolines / chemistry
  • Isoquinolines / metabolism*
  • Male
  • Molecular Structure
  • Positron-Emission Tomography / methods
  • Pyrazoles / agonists*
  • Pyrazoles / chemistry
  • Pyrazoles / metabolism*
  • Pyrimidines / agonists*
  • Pyrimidines / chemistry
  • Pyrimidines / metabolism*
  • Radioligand Assay
  • Radiopharmaceuticals / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism*

Substances

  • Acetamides
  • Carbon Radioisotopes
  • Carrier Proteins
  • Fluorine Radioisotopes
  • Isoquinolines
  • N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
  • N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide
  • Pyrazoles
  • Pyrimidines
  • Radiopharmaceuticals
  • Receptors, GABA-A
  • Tspo protein, rat
  • PK 11195