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

BackgroundActivation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [11C]-(R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [11C]-(R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [11C]-DPA-713 and [18F]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis.Materials and MethodsRats were intranasally inoculated with HSV-1. On day 6 or 7 after inoculation, small animal PET studies were performed to compare [11C]-(R)-PK11195, [11C]-DPA-713, and [18F]-DPA-714.ResultsUptake of [11C]-DPA-713 in infected brain areas was comparable to that of [11C]-(R)-PK11195, but [11C]-DPA-713 showed lower non-specific binding. Non-specific uptake of [18F]-DPA-714 was lower than that of [11C]-(R)-PK11195. In the infected brain, total [18F]-DPA-714 uptake was lower than that of [11C]-(R)-PK11195, with comparable specific uptake.Conclusions[11C]-DPA-713 may be more suitable for visualizing mild inflammation than [11C]-(R)-PK11195. In addition, the fact that [18F]-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.