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

Introduction: Many neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [C-11]-PK11195 can be used to study neuroinflammation in these disorders. However; [C-11]-PK11195 may not be sensitive enough to visualize mild neuroinflammation. As a potentially more sensitive PET tracer for neuroinflammation, [C-11]-N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)-acetamide (DAA1106) was evaluated in a rat model of herpes encephalitis. Methods: Male Wistar rats were intranasally inoculated with HSV-1 (HSE) or phosphate-buffered saline (control). At Day 6 or Day 7 after inoculation, small-animal [C-11]-DAA1106 PET scans were acquired, followed by ex vivo biodistribution. Arterial blood sampling was performed for quantification of uptake. Results: In HSE rats, a significantly higher ex vivo, but not in vivo, uptake of [C-11]-DAA1106 was found in almost all examined brain areas (24-71%, P<.05), when compared to control rats. Pretreatment with unlabeled PK11195 effectively reduced [C-11]-DAA1106 uptake in HSE rats (54-84%; P<.001). The plasma and brain time-activity curves showed rapid uptake of [C-11]-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: [C-11]-DAA1106 showed a high and specific ex vivo uptake in the encephalitic rat brain. However, neuroinflammation could not be demonstrated in vivo by [C-11]-DAA1106 PET. Quantification of the uptake of [C-11]-DAA1106 using plasma sampling is not optimal, due to rapid tissue uptake, slow tissue clearance and low plasma activity. (C) 2010 Elsevier Inc. All rights reserved.