In vivo mapping of vascular inflammation using the translocator protein tracer 18F-FEDAA1106.
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 18F-FEDAA1106 and 2-deoxy-2-[18F]fluoro-d-glucose (18F-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 18F-FEDAA1106 or 18F-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 18F-FEDAA1106 (p < .01) or FDG (p < .05). However, the 18F-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 18F-FEDAA1106 can be used in vivo for detection of vascular inflammation. Moreover, the signal pattern of 18F-FEDAA1106 corresponded with vascular inflammation more specifically than FDG uptake.
Simon
S
Cuhlmann
Willy
W
Gsell
Kim
K
Van der Heiden
Josef
J
Habib
Jordi L
JL
Tremoleda
Magdy
M
Khalil
Federico
F
Turkheimer
Merlijn J
MJ
Meens
Brenda R
BR
Kwak
Joseph
J
Bird
Anthony P
AP
Davenport
John
J
Clark
Dorian
D
Haskard
Rob
R
Krams
Hazel
H
Jones
Paul C
PC
Evans
D000081:Acetamides / Q000378:metabolism; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism
D000081:Acetamides; C475621:N-(5-fluoro-2-phenoxyphenyl)-N-(2-fluoroethyl-5-methoxybenzyl)acetamide; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18