Uptake of inflammatory cell marker [11C]PK11195 into mouse atherosclerotic plaques.
OBJECTIVE
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.
Laitinen
Iina
I
Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland. iina.laitinen@tyks.fi
Marjamäki
Päivi
P
Någren
Kjell
K
Laine
V Jukka O
VJ
Wilson
Ian
I
Leppänen
Pia
P
Ylä-Herttuala
Seppo
S
Roivainen
Anne
A
Knuuti
Juhani
J
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D001345:Autoradiography; D015415:Biomarkers / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry; D005240:Feasibility Studies; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D014018:Tissue Distribution
D015415:Biomarkers; D002250:Carbon Radioisotopes; D007546:Isoquinolines; C037850:PK 11195