Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 positron emission tomography/computed tomography

We sought to determine whether intraplaque inflammation could be measured with positron emission tomography/computed tomography angiography (PET/CTA) using C-11-PK11195, a selective ligand of the translocator protein (18 kDa) (TSPO) which is highly expressed by activated macrophages. Patients (n 32; mean age 70 9 years) with carotid stenoses (n 36; 9 symptomatic and 27 asymptomatic) underwent C-11-PK11195 PET/CTA imaging. C-11-PK11195 uptake into carotid plaques was measured using target-to-background ratios (TBR). On CTA images, plaque composition was assessed by measuring CT attenuation of the carotid plaque. Eight patients underwent carotid endarterectomy and ultrathin contiguous sections were processed for TSPO and CD68 (using immunohistochemical staining, H-3-PK11195 autoradiography, and confocal fluorescence microscopy). Carotid plaques associated with ipsilateral symptoms (stroke or transient ischaemic attack) had higher TBR (1.06 0.20 vs. 0.86 0.11, P 0.001) and lower CT attenuation [(median, inter-quartile range) 37, 2440 vs. 71, 56125 HU, P 0.01] than those without. On immunohistochemistry and confocal fluorescence microscopy, CD68 and PBR co-localized with H-3-PK11195 uptake at autoradiography. There was a significant correlation between C-11-PK11195 TBR and autoradiographic percentage-specific binding (r 0.77, P 0.025). Both TBR and CT plaque attenuation had high negative predictive values (91 and 92, respectively) for detecting symptomatic patients. However, the best positive predictive value (100) was achieved when TBR and CT attenuation were combined. Imaging intraplaque inflammation in vivo with C-11-PK11195 PET/CTA is feasible and can distinguish between recently symptomatic and asymptomatic plaques. Patients with a recent ischaemic event had ipsilateral plaques with lower CT attenuation and increased C-11-PK11195 uptake.