Uptake of inflammatory cell marker [11C]PK11195 into mouse atherosclerotic plaques

Purpose The ligand [ 11 C]PK11195 binds with high affinity and selectivity to peripheral benzodiazepine receptor, expressed in high amounts in macrophages. In humans, [ 11 C]PK11195 has been used successfully for the in vivo imaging of inflammatory processes of brain tissue. The purpose of this study was to explore the feasibility of [ 11 C]PK11195 in imaging inflammation in the atherosclerotic plaques. Methods The presence of PK11195 binding sites in the atherosclerotic plaques was verified by examining the in vitro binding of [ 3 H]PK11195 onto mouse aortic sections. Uptake of intravenously administered [ 11 C]PK11195 was studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48 atherosclerotic mice. Accumulation of the tracer was compared between the atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography and histological analyses. Results The [ 3 H]PK11195 was found to bind to both the atherosclerotic plaques and the healthy wall. The autoradiography analysis revealed that the uptake of [ 11 C]PK11195 to inflamed regions in plaques was more prominent ( p = 0.011) than to non-inflamed plaque regions, but overall it was not higher than the uptake to the healthy vessel wall. Also, the accumulation of 11 C radioactivity into the aorta of the atherosclerotic mice was not increased compared to the healthy control mice. Conclusions Our results indicate that the uptake of [ 11 C]PK11195 is higher in inflamed atherosclerotic plaques containing a large number of inflammatory cells than in the non-inflamed plaques. However, the tracer uptake to other structures of the artery wall was also prominent and may limit the use of [ 11 C]PK11195 in clinical imaging of atherosclerotic plaques.