Comparison of 18F-fluoro-deoxy-glucose, 18F-fluoro-methyl-choline, and 18F-DPA714 for positron-emission tomography imaging of leukocyte accumulation in the aortic wall of experimental abdominal aneurysms.
OBJECTIVE
Abdominal aortic aneurysm (AAA) is a frequent form of atherothrombotic disease, whose natural history is to enlarge and rupture. Indicators other than AAA diameter would be useful for preventive surgery decision-making, including positron-emission tomography (PET) methods permitting visualization of aortic wall leukocyte activation relevant to prognostic AAA evaluation. In this study, we compare three PET tracers of activated leukocytes, 18F-fluoro-deoxy-glucose (FDG), 18F-fluoro-methyl-choline (FCH), and 18F-DPA714 (a peripheral benzodiazepine receptor antagonist) for in vivo PET quantification of aortic wall inflammation in rat experimental AAAs, in correlation with histopathological studies of lesions.


METHODS
AAAs were induced by orthotopic implantation of decellularized guinea pig abdominal aorta in 46 Lewis rats. FDG-PET (n = 20), FCH-PET (n = 8), or both (n = 12) were performed 2 weeks to 4 months after the graft, 1 hour after tracer injection (30 MBq). Six rats (one of which had FDG-PET) underwent 18F-DPA714-PET. Rats were sacrificed after imaging; AAAs and normal thoracic aortas were cut into axial sections for quantitative autoradiography and histologic studies, including ED1 (macrophages) and CD8 T lymphocyte immunostaining. Ex vivo staining of AAAs and thoracic aortas with 18F-DPA714 and unlabeled competitors was performed.


RESULTS
AAAs developed in 35 out of 46 cases. FCH uptake in AAAs was lower than that of FDG in all cases on imaging, with lower AAA-to-background maximal standardized uptake value (SUV(max)) ratios (1.78 ± 0.40 vs 2.71 ± 0.54; P < .01 for SUV(max) ratios), and lower AAA-to-normal aorta activity ratios on autoradiography (3.52 ± 1.26 vs 8.55 ± 4.23; P < .005). FDG AAA-to-background SUV(max) ratios correlated with the intensity of CD8 + ED1 staining (r = .76; P < .03). FCH AAA-to-background SUV(max) ratios correlated with the intensity of ED1 staining (r = .80; P < .03). 18F-DPA714 uptake was similar in AAAs and in normal aortas, both in vivo and ex vivo.


CONCLUSIONS
In rat experimental AAA, characterized by an important aortic wall leukocytes activity, FDG-PET showed higher sensitivity than FCH-PET and 18F-DPA714-PET to detect activated leukocytes. This enhances potential interest of this tracer for prognostic evaluation of AAA in patients.
Institut National de la Santé et de la Recherche Médicale Unit 698, Paris, France. laure.sarda@inserm.fr
Laure
L
Sarda-Mantel
Jean-Marc
JM
Alsac
Raphaël
R
Boisgard
Florence
F
Hervatin
Françoise
F
Montravers
Bertrand
B
Tavitian
Jean-Baptiste
JB
Michel
Dominique
D
Le Guludec
D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D001345:Autoradiography; D002634:Chemotaxis, Leukocyte; D002794:Choline / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D006168:Guinea Pigs; D007962:Leukocytes / Q000000981:diagnostic imaging* / Q000276:immunology; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D051381:Rats; D011917:Rats, Inbred Lew; D012680:Sensitivity and Specificity; D014183:Transplantation, Heterologous
C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; C516370:fluoromethylcholine; D019788:Fluorodeoxyglucose F18; D002794:Choline