Evaluation of [11C]-DAA1106 for imaging and quantification of neuroinflammation in a rat model of herpes encephalitis.
BACKGROUND
Many neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [(11)C]-PK11195 can be used to study neuroinflammation in these disorders. However, [(11)C]-PK11195 may not be sensitive enough to visualize mild neuroinflammation. As a potentially more sensitive PET tracer for neuroinflammation, [(11)C]-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 [(11)C]-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 [(11)C]-DAA1106 was found in almost all examined brain areas (24-71%, P<.05), when compared to control rats. Pretreatment with unlabeled PK11195 effectively reduced [(11)C]-DAA1106 uptake in HSE rats (54-84%; P<.001). The plasma and brain time-activity curves showed rapid uptake of [(11)C]-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
[(11)C]-DAA1106 showed a high and specific ex vivo uptake in the encephalitic rat brain. However, neuroinflammation could not be demonstrated in vivo by [(11)C]-DAA1106 PET. Quantification of the uptake of [(11)C]-DAA1106 using plasma sampling is not optimal, due to rapid tissue uptake, slow tissue clearance and low plasma activity.
Doorduin
Janine
J
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.doorduin@ngmb.umcg.nl
Klein
Hans C
HC
de Jong
Johan R
JR
Dierckx
Rudi A
RA
de Vries
Erik F J
EF
D000081:Acetamides / Q000493:pharmacokinetics; D000818:Animals; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology*; D018259:Herpesvirus 1, Human / Q000502:physiology; D007249:Inflammation / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D010647:Phenyl Ethers / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000081:Acetamides; C118942:DAA 1106; D010647:Phenyl Ethers