Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE−/− mice

Zhao, Yan; Kuge, Yuji; Zhao, Shen; Morita, Koichi; Inubushi, Masayuki; Strausś, H. William; Blankenberg, Francis G.; Tamaki, Nagara

doi:10.1007/s00259-007-0433-2

Cited by 41 publications

(38 citation statements)

References 41 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, concerns over target specificity, rate of clearance from off-target tissues, efficiency of plaque penetration, and image intensity may limit use of monoclonal antibodies in these imaging applications (4,6,35,36). Finally, lipid-binding proteins such as annexin A5 (7,37) that recognize exposed phosphatidylserine on apoptotic cells can also be exploited to image dying cells, including apoptotic macrophage foam cells in atherosclerotic lesions. However, because phosphatidylserine can be exposed on any dying or damaged cell, including activated platelets; ischemic, stressed, or traumatized cardiomyocytes; myoblasts; immune cells; and erythrocytes (38,39), opportunities for misinterpretation of data once again arise.…”

Section: Discussionmentioning

confidence: 99%

“…Attempts to quantitate these differences as a means of assessing cardiovascular risk have focused on the design of noninvasive imaging agents that detect the accumulation of immune cells (4), expression of metalloproteinase activity (5), heightened consumption of glucose (6), and apoptosis of cells within the vascular bed (7). Although such strategies show considerable promise for identification of vulnerable plaque, they also suffer from some degree of nonspecificity because each strategy also images healthy cells involved in other processes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Ayala-López¹,

Xia²,

Varghese³

et al. 2010

J Nucl Med

View full text Add to dashboard Cite

Early detection of heart disease is essential for the implementation of intervention strategies that reduce the risk of cardiovascular events. Radioimaging methods that have been explored for this purpose include 18 F-FDG, which measures sites of elevated metabolic activity; 99m Tc-annexin A5, which reveals regions of enhanced apoptosis and thrombosis; and 99m Tc-labeled antilectinlike oxidized low-density lipoprotein receptor 1 antibody, which detects the lectinlike oxidized low-density lipoprotein receptor 1 that is overexpressed on a variety of vasculatureassociated cells. In this study, we examine the use of a folatetargeted chelate of 99m Tc, termed 99m Tc-EC20, for imaging of folate receptor (FR)-expressing macrophages that accumulate in atherosclerotic plaques, internalize cholesterol-rich lipoprotein particles, and evolve into foam cells that form components of vulnerable atherosclerotic lesions. Methods: 99m Tc-EC20 was injected into apoliprotein E knockout (apoE2/2) mice fed a normal or Western (high-fat) diet for 25 wk and imaged by g-scintigraphy. Treated mice were also dissected, and radioactivities in excised aortas were quantified by g-counting and imaged by autoradiography. The role of FR-expressing macrophages in uptake of 99m Tc-EC20 was also examined by comparing images of apoE2/2 mice before and after treatment with clodronate liposomes to deplete tissue macrophages, comparing the sites of 99m Tc-EC20 enrichment with sites of macrophage accumulation in thin sections of atherosclerotic tissues, and examining the expression of FRs on atherosclerotic plaquederived macrophages by flow cytometry. Results: ApoE2/2 mice on Western chow exhibited significantly greater accumulation of 99m Tc-EC20 in atherosclerotic lesions than their counterparts on normal chow. The aortas of apoE2/2 mice on a Western diet demonstrated greater numbers of FR-positive macrophages by flow cytometry than did those of apoE2/2 mice on a normal diet. Clodronate liposome treatment significantly reduced the accumulation of 99m Tc-EC20 in atherosclerotic tissues, suggesting that macrophages or monocytes are responsible for uptake of the folate-linked radioimaging agent. Histologic and autoradiographic analysis of tissue sections demonstrated that macrophage accumulation correlated with regions of 99m Tc-EC20 uptake. Conclusion: 99m Tc-EC20 can be used for the imaging of atherosclerosis by selectively targeting FR-positive activated macrophages.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Ayala-López¹,

Xia²,

Varghese³

et al. 2010

J Nucl Med

View full text Add to dashboard Cite

show abstract

“…After radioactivity counting was complete, aortic specimens were longitudinally incised, mounted on clean glass slides, and stained with Oil Red O (Sigma) by use of the following protocol (20). In brief, each specimen was rinsed in 60% 2-propanol for 3 min, incubated in Oil Red O solution at 37°C for 40 min, destained in 60% 2-propanol for 6 min, and then mounted on a glass slide with aqueous mounting medium (Biomeda Corp.).…”

Section: Evaluation Of Atherosclerotic Lesionsmentioning

confidence: 99%

“…Oil Red O staining and immunohistochemical staining with a mouse macrophage-specific antibody (Mac-2, clone m3/38; Cedarlane) were performed by use of standard procedures (20) with 5-mm-thick cryostat cross sections of aortic tissues from 4 additional mice at 25 wk of age in each group (ChD-apoE 2/2 , ChD-wild-type, and normal diet-wild-type mice) to confirm the presence of atherosclerotic disease (Fig. 1) and macrophage infiltration (Supplemental Fig.…”

Section: Evaluation Of Atherosclerotic Lesionsmentioning

confidence: 99%

Prolonged High-Fat Feeding Enhances Aortic ¹⁸F-FDG and ^99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice

Zhao

Kuge²,

Strausś³

et al. 2008

J Nucl Med

Self Cite

View full text Add to dashboard Cite

18 F-FDG, a marker of the enhanced metabolism characteristic of activated inflammatory cells, and 99m Tc-annexin A5, a marker of apoptosis, are both widely believed to be useful for the imaging of unstable atheroma (rupture-prone vulnerable plaques [VP]). Serum cholesterol functions as a proinflammatory factor, driving the formation of VP, and affects the immune responses of aortic tissues systemically. It is therefore reasonable to postulate that prolonged cholesterol loading may alter the aortic uptake of these tracers. Here, we evaluated the aortic uptake of 18 F-FDG and 99m Tc-annexin A5 in apolipoprotein E-deficient (apoE 2/2 ) and wild-type mice placed on high-fat diets. Methods: Male apoE 2/2 and wild-type (C57BL/6J) mice were maintained on high-fat diets after the age of 5 wk. Wild-type mice fed regular chow were used as controls. At the ages of 10, 18, and 25 wk (5-15 mice per group at each time point), mice were injected with 18 F-FDG or 99m Tc-annexin A5 after 12 h of fasting. At 1 h after 18 F-FDG injection (or 2 h after 99m Tc-annexin A5 injection), mice were sacrificed, and the aortas were removed for welltype scintillation counting of radioactivity. The results were expressed as percentage injected dose per gram of tissue and normalized by animal body weight [(ID%/g) · kg]. En face staining was then performed to assess the location and size (surface area) of the lipid pool within each aortic specimen. Concurrent blood samples were obtained to determine the plasma lipid profile of each group. Results: No atherosclerotic lesions were found in wild-type mice regardless of the diet, whereas the lesion area progressively increased with age in apoE 2/2 mice. Mean plasma cholesterol levels remained stable with the regular diet in wild-type mice (73-78 mg/dL) but increased with cholesterol feeding in wild-type mice (143-179 mg/dL) and in apoE 2/2 mice (.1,300 mg/dL). Aortic tracer uptake [(ID%/g) · kg] remained stable with the regular diet in wild-type mice (0.054-0.053 and 0.021-0.023 for 99m Tc-annexin A5) but increased with cholesterol feeding in wild-type mice (0.164 for 18 F-FDG and 0.036 for 99m Tc-annexin A5 at 25 wk) and in apoE 2/2 mice (0.249 for 18 F-FDG and 0.047 for 99m Tc-annexin A5 at 25 wk). Conclusion:The accumulation of 18 F-FDG and 99m Tc-annexin A5 in aortic tissues is influenced not only by the progression of atherosclerotic disease but also by cholesterol loading over time.

show abstract

“…Immunohistochemical staining of the serial sections with a mouse macrophage-specific antibody (Mac-2, clone m3/38, Cedarlane, Ontario, Canada) was performed in accordance with a previously reported immunohistochemical procedure [11]. The TSP4 immunohistochemical staining of the serial sections was performed as shown below.…”

Section: Histochemical Studymentioning

confidence: 99%

Radioimmunodetection of Atherosclerotic Lesions Focusing on the Accumulation Mechanism of Immunoglobulin G

Shimizu

Hanzawa

Zhao

et al. 2016

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

Self Cite

View full text Add to dashboard Cite

In the diagnosis of atherosclerosis, detailed evaluation of biomarkers related to its lesion formation is desired for estimation of its progression rate. In our previous proteomic studies of atherosclerosis mice, the protein level of thrombospondin-4 (TSP4) in the aorta, but not in plasma, elevated relatively with atherosclerotic plaque formation. Therefore, we supposed that TSP4 would be a potential biomarker for diagnostic imaging of atherosclerotic progression. Immunoglobulin G (IgG) has been widely used as a basic molecule of imaging probes providing images specific to their target biomolecules, owing to the antigenantibody reaction. Therefore, we first developed anti-TSP4 monoclonal IgG radiolabeled with 99m Tc ( 99m Tc-TSP4-mAb). 99m Tc-TSP4-mAb showed higher accumulation in atherosclerotic aortas of apoE À/À

show abstract

Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE−/− mice

Abstract: Annexin A5 and FDG Uptake in ApoE-/-Mice

Cited by 41 publications

References 41 publications

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Prolonged High-Fat Feeding Enhances Aortic ¹⁸F-FDG and ^99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice

Radioimmunodetection of Atherosclerotic Lesions Focusing on the Accumulation Mechanism of Immunoglobulin G

Contact Info

Product

Resources

About

Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE−/− mice

Abstract: Annexin A5 and FDG Uptake in ApoE-/-Mice

Cited by 41 publications

References 41 publications

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Imaging of Atherosclerosis in Apoliprotein E Knockout Mice: Targeting of a Folate-Conjugated Radiopharmaceutical to Activated Macrophages

Prolonged High-Fat Feeding Enhances Aortic 18F-FDG and 99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice

Radioimmunodetection of Atherosclerotic Lesions Focusing on the Accumulation Mechanism of Immunoglobulin G

Contact Info

Product

Resources

About

Prolonged High-Fat Feeding Enhances Aortic ¹⁸F-FDG and ^99mTc-Annexin A5 Uptake in Apolipoprotein E-Deficient and Wild-Type C57BL/6J Mice