[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.

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.

• Authors: Janine Doorduin, Hans C Klein, Rudi A Dierckx, Michelle James, Michael Kassiou, Erik F J de Vries
• Journal: Molecular imaging and biology (Mol Imaging Biol) 2009 Nov-Dec Vol. 11 Issue 6 Pg. 386-98 ISSN: 1860-2002 [Electronic] United States
• PMID: 19330384 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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