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.

Abstract

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.

• Authors: Laure Sarda-Mantel, Jean-Marc Alsac, Raphaël Boisgard, Florence Hervatin, Françoise Montravers, Bertrand Tavitian, Jean-Baptiste Michel, Dominique Le Guludec
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 56 Issue 3 Pg. 765-73 (Sep 2012) ISSN: 1097-6809 [Electronic] United States
• PMID: 22726755 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Chemical References

• N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
• Pyrazoles
• Pyrimidines
• Radiopharmaceuticals
• fluoromethylcholine
• Fluorodeoxyglucose F18
• Choline

Topics

• Animals
• Aorta, Abdominal (diagnostic imaging, immunology, pathology, transplantation)
• Aortic Aneurysm, Abdominal (diagnostic imaging, etiology, immunology, pathology)
• Autoradiography
• Chemotaxis, Leukocyte
• Choline (analogs & derivatives)
• Disease Models, Animal
• Fluorodeoxyglucose F18
• Guinea Pigs
• Leukocytes (diagnostic imaging, immunology)
• Positron-Emission Tomography
• Predictive Value of Tests
• Pyrazoles
• Pyrimidines
• Radiopharmaceuticals
• Rats
• Rats, Inbred Lew
• Sensitivity and Specificity
• Transplantation, Heterologous