title: Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis.
abstract: Macrophage presence within atherosclerotic plaque is a feature of instability and a risk factor for plaque rupture and clinical events. Activated macrophages express high levels of the translocator protein/peripheral benzodiazepine receptor (TSPO/PBR). In this study, we investigated the potential for quantifying plaque inflammation by targeting this receptor. TSPO expression and distribution in the plaque were quantified using radioligand binding assays and autoradiography. We show that cultured human macrophages expressed 20 times more TSPO than cultured human vascular smooth muscle cells (VSMCs), the other abundant cell type in plaque. The TSPO ligands [3H](R)-1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([3H](R)-PK11195) and [3H]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([3H]-DAA1106) bound to the same sites in human carotid atherosclerotic plaques in vitro, and demonstrated significant correlation with macrophage-rich regions. In conclusion, our data indicate that radioisotope-labelled DAA1106 has the potential to quantify the macrophage content of atherosclerotic plaque.
authors.affiliation: Clinical Pharmacology Unit, Addenbrooke's Hospital, and Clinical Neurosciences, University of Cambridge, Hills Road, Cambridge CB2 0QQ, United Kingdom. jleb2@wbic.cam.ac.uk
authors.forename: J L E
authors.initials: JL
authors.lastname: Bird
authors.forename: D
authors.initials: D
authors.lastname: Izquierdo-Garcia
authors.forename: J R
authors.initials: JR
authors.lastname: Davies
authors.forename: J H F
authors.initials: JH
authors.lastname: Rudd
authors.forename: K C
authors.initials: KC
authors.lastname: Probst
authors.forename: N
authors.initials: N
authors.lastname: Figg
authors.forename: J C
authors.initials: JC
authors.lastname: Clark
authors.forename: P L
authors.initials: PL
authors.lastname: Weissberg
authors.forename: A P
authors.initials: AP
authors.lastname: Davenport
authors.forename: E A
authors.initials: EA
authors.lastname: Warburton
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology*; D003251:Constriction, Pathologic / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018079:Receptors, GABA / Q000737:chemistry / Q000502:physiology*; D011963:Receptors, GABA-A / Q000737:chemistry / Q000502:physiology*
chemical_list: D007546:Isoquinolines; D008024:Ligands; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C499229:TSPO protein, human; D019788:Fluorodeoxyglucose F18; C037850:PK 11195