Evaluation of [11C]-DAA1106 for imaging and quantification of neuroinflammation in a rat model of herpes encephalitis

IntroductionMany neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [11C]-PK11195 can be used to study neuroinflammation in these disorders. However, [11C]-PK11195 may not be sensitive enough to visualize mild neuroinflammation. As a potentially more sensitive PET tracer for neuroinflammation, [11C]-N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)-acetamide (DAA1106) was evaluated in a rat model of herpes encephalitis.MethodsMale Wistar rats were intranasally inoculated with HSV-1 (HSE) or phosphate-buffered saline (control). At Day 6 or Day 7 after inoculation, small-animal [11C]-DAA1106 PET scans were acquired, followed by ex vivo biodistribution. Arterial blood sampling was performed for quantification of uptake.ResultsIn HSE rats, a significantly higher ex vivo, but not in vivo, uptake of [11C]-DAA1106 was found in almost all examined brain areas (24–71%, P<.05), when compared to control rats. Pretreatment with unlabeled PK11195 effectively reduced [11C]-DAA1106 uptake in HSE rats (54–84%; P<.001). The plasma and brain time–activity curves showed rapid uptake of [11C]-DAA1106 into tissue. The data showed a good fit to the Logan analysis but could not be fitted to a two-tissue compartment model.Conclusions[11C]-DAA1106 showed a high and specific ex vivo uptake in the encephalitic rat brain. However, neuroinflammation could not be demonstrated in vivo by [11C]-DAA1106 PET. Quantification of the uptake of [11C]-DAA1106 using plasma sampling is not optimal, due to rapid tissue uptake, slow tissue clearance and low plasma activity.