[11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson's disease?
[(11)C]-PK11195 PET has been used for in vivo brain imaging of microglia activation in Parkinson's disease (PD) patients. COX-2 inhibition has been shown to reduce neuroinflammation and neurodegeneration in animal models of PD. This pilot study assessed the use of [(11)C]-PK11195 PET to quantify neuroinflammation and evaluate the ability of COX-2 inhibition to reduce neuroinflammation in PD patients.


METHODS
Fourteen PD patients and eight healthy, age matched controls underwent a [(11)C]-PK11195 PET and MRI scan. Five PD patients were scanned before and after one month of celecoxib treatment 200 mg/day. Arterial plasma sampling and metabolite analysis were performed to create plasma input curves. A 2-compartment model and Logan analysis were applied and parametric DV images were compared using t-test in SPM2. In addition a simplified reference region model (SRTM) was applied, with both the cerebellum and a reference region derived from cluster analysis.


RESULTS
Using the cluster analysis, PD patients showed higher contralateral putamen BP and midbrain BP compared to controls, although considerable overlap was seen and differences were not statistically significant. Unexpectedly, BP and DV after celecoxib were slightly higher. Cerebellum as reference region resulted in lower BP values and k(3)/k(4) gave 10-fold higher BP values. Linearization of the data did not show differences between PD patients and controls.


CONCLUSIONS
In current practice, [(11)C]-PK11195 seems an unsuitable tracer for accurate or reliable quantification of neuroinflammation. Refinement of [(11)C]-PK11195 uptake analysis and, more importantly, further development of better tracers is necessary to enable accurate measurement of neuroinflammation and effects of anti-inflammatory treatment in patients.
Bartels
A L
AL
Department of Neurology, University Medical Centre Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Willemsen
A T M
AT
Doorduin
J
J
de Vries
E F J
EF
Dierckx
R A
RA
Leenders
K L
KL
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D001931:Brain Mapping; D016022:Case-Control Studies; D000068579:Celecoxib; D016000:Cluster Analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007546:Isoquinolines; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods; D011720:Pyrazoles / Q000097:blood / Q000627:therapeutic use*; D013449:Sulfonamides / Q000097:blood / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D052246:Cyclooxygenase 2 Inhibitors; D007546:Isoquinolines; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; C037850:PK 11195