RT Journal Article
SR Electronic
T1 Evaluation of Apoptosis with <sup>99m</sup>Tc-rhAnnexin V-128 and Inflammation with <sup>18</sup>F-FDG in a Low-Dose Irradiation Model of Atherosclerosis in Apolipoprotein E–Deficient Mice
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1784
OP 1791
DO 10.2967/jnumed.116.172346
VO 57
IS 11
A1 Maryam Kamkar
A1 Lihui Wei
A1 Chantal Gaudet
A1 Michelle Bugden
A1 Julia Petryk
A1 Yin Duan
A1 Heather M. Wyatt
A1 R. Glenn Wells
A1 Yves L. Marcel
A1 Nicholas D. Priest
A1 Ronald E.J. Mitchel
A1 Terrence D. Ruddy
YR 2016
UL http://jnm.snmjournals.org/content/57/11/1784.abstract
AB Low-dose radiation in apolipoprotein E–deficient (ApoE−/−) mice has a protective effect with less subsequent atherosclerosis. Inflammation and apoptosis play major roles in the development of atherosclerosis. We evaluated the temporal pattern of the development of histologic atherosclerosis, inflammation with 18F-FDG, and apoptosis with 99mTc-rhAnnexin V-128 at 3 time points. Methods: ApoE−/− mice were fed a high-fat diet, exposed to low-dose 60Co γ-radiation of 25 mGy at 2 mo of age, and evaluated within 1 wk (2-mo group), 1 mo (3-mo group), and 2 mo (4-mo group) from the time of radiation. Mice were divided into 3 subgroups and each received 18F-FDG, 99mTc-rhAnnexin V-128, or no radiotracer for autoradiography. Mice underwent euthanasia and aortic root dissection. The extent of atherosclerosis was determined by en face and Oil red O imaging. Aortic arch inflammation (18F-FDG) and apoptosis (99mTc-rhAnnexin V-128) were determined with digital autoradiography. Aortic sinus sections were stained with Sudan IV for assessment of lesion area and stage, antiCD68 antibody for inflammation and anti–cleaved-caspase 3 antibody for apoptosis. Results: The extent of aortic atherosclerosis increased from 2 to 3 mo and from 3 to 4 mo. Inflammation (CD68) decreased and apoptosis (anti–cleaved-caspase 3 antibody) increased in aortic sinus slices measured as percentage of lesion by 4 mo. With increasing lesion stage, lesion inflammation decreased and lesion apoptosis increased. Aortic arch inflammation (18F-FDG uptake) did not differ over time and did not correlate with average lesion stage. However, aortic arch apoptosis (99mTc-rhAnnexin V-128) increased significantly by 4 mo and correlated with average lesion stage. There were no differences between the treatment subgroups (18F-FDG, 99mTc-rhAnnexin V-128, or no radiotracer). Conclusion: The temporal pattern of development of inflammation and apoptosis differ during the development of atherosclerosis in ApoE−/− mice treated with low-dose radiation. Advanced lesions are characterized by increased apoptosis and either less or similar amounts of inflammation, shown on immunohistochemistry and autoradiography. Treatment with radiotracers had no significant effects on extent of atherosclerosis, inflammation, or apoptosis.