In Vivo Mapping of Vascular Inflammation Using the Translocator Protein Tracer F-FEDAA1106

Abstract

Noninvasive imaging methods are required to monitor the inflammatory content of atherosclerotic plaques. FEDAA1106 (N-(5-fluoro- 2-phenoxyphenyl)- N -(2-(2-fluoroethoxy)-5-methoxybenzyl) acetamide) is a selective ligand for TSPO-18kDa (also known as peripheral benzodiazepine receptor), which is expressed by activated macrophages. We compared 18 F-FEDAA1106 and 2-deoxy-2-[ 18 F]fluoro-D- glucose ( 18 F-FDG, a marker of glucose metabolism) for positron emission tomographic (PET) imaging of vascular inflammation. This was tested using a murine model in which focal inflammation was induced in the carotid artery via placement of a constrictive cuff. Immunostaining revealed CD68-positive cells (macrophages) at a disturbed flow site located downstream from the cuff. Dynamic PET imaging using 18 F-FEDAA1106 or 18 F-FDG was registered to anatomic data generated by computed tomographic (CT)/CT angiography. Standardized uptake values were significantly increased at cuffed compared to contralateral arteries using either 18 F-FEDAA1106 ( p < .01) or FDG ( p < .05). However, the 18 F-FEDAA1106 signal was significantly higher at the inflamed disturbed flow region compared to the noninflamed uniform flow regions, whereas differences in FDG uptake were less distinct. We conclude that 18 F-FEDAA1106 can be used in vivo for detection of vascular inflammation. Moreover, the signal pattern of 18 F-FEDAA1106 corresponded with vascular inflammation more specifically than FDG uptake.