Imaging of vascular inflammation with [11C]-PK11195 and positron emission tomography/computed tomography angiography.
OBJECTIVE
We sought to investigate whether positron emission tomography/computed tomography (CT) angiography using [11C]-PK11195, a selective ligand for peripheral benzodiazepine receptors expressed in activated macrophages, can be used to image vascular inflammation.


BACKGROUND
Activated macrophages and T lymphocytes are fundamental elements in the pathogenesis of large-vessel vasculitides.


METHODS
Fifteen patients (age 52+/-16 years) with systemic inflammatory disorders (6 consecutive symptomatic patients with clinical suspicion of active vasculitis and 9 asymptomatic control patients) underwent positron emission tomography with [11C]-PK11195 and CT angiography. [11C]-PK11195 uptake was measured by calculating target-to-background ratios of activity normalized to venous blood.


RESULTS
Coregistration of positron emission tomography with contrast-enhanced CT angiography facilitated localization of [11C]-PK11195 arterial wall uptake. Visual analysis revealed focal [11C]-PK11195 uptake in the arterial wall of all 6 symptomatic patients, but in none of the asymptomatic controls. Although serum inflammatory biomarkers (C-reactive protein, erythrocyte sedimentation rate, white cell count) did not differ significantly between the 2 groups, symptomatic patients had increased [11C]-PK11195 vascular uptake (target-to-background ratio 2.41+/-1.59 vs. 0.98+/-0.10; p=0.001).


CONCLUSIONS
By binding to activated macrophages in the vessel wall, [11C]-PK11195 enables noninvasive imaging of vascular inflammation. Alternative longer-lived radioligands for probing peripheral benzodiazepine receptors are being tested for wider clinical applications.
Pugliese
Francesca
F
Medical Research Council Clinical Sciences Centre and National Heart and Lung Institute, Imperial College, and Hammersmith Hospital, London, United Kingdom.
Gaemperli
Oliver
O
Kinderlerer
Anne R
AR
Lamare
Frederic
F
Shalhoub
Joseph
J
Davies
Alun Huw
AH
Rimoldi
Ornella E
OE
Mason
Justin C
JC
Camici
Paolo G
PG
D000328:Adult; D000368:Aged; D000792:Angiography; D001158:Arteries / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes; D005260:Female; D013700:Giant Cell Arteritis / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007546:Isoquinolines / Q000493:pharmacokinetics; D008180:Lupus Erythematosus, Systemic / Q000000981:diagnostic imaging; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A / Q000378:metabolism; D013625:Takayasu Arteritis / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed; D014657:Vasculitis / Q000000981:diagnostic imaging*
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C037850:PK 11195