Abstract:
PURPOSE:Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis. PROCEDURES:Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [99mTc]IgG. ApoE-/- or C57BL/6J mice were injected intravenously with [99mTc]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [99mTc]IgG. The radioactivities in the cells were measured after 1 h of incubation. [99mTc]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fcγ receptor (FcγR) antibody. The expression levels of FcγRs in the cells were measured by western blot analysis. RESULTS:[99mTc]IgG accumulation levels in the aortas were significantly higher in apoE-/- mice than in C57BL/6J mice (5.1 ± 1.4 vs 2.8 ± 0.5 %ID/g, p < 0.05). Autoradiographic images showed that the accumulation areas highly correlated with the macrophage-infiltrated areas. M1 macrophages showed significantly higher levels of [99mTc]IgG than M2 or M0 (nonpolarized) macrophages [2.2 ± 0.3 (M1) vs 0.5 ± 0.1 (M2), 0.4 ± 0.1 (M0) %dose/mg protein, p < 0.01] and higher expression levels of FcγRI and FcγRII. [99mTc]IgG accumulation in M1 macrophages was suppressed by pretreatment with the anti-FcγR antibody [2.2 ± 0.3 (nonpretreatment) vs 1.2 ± 0.2 (pretreatment) %ID/mg protein, p < 0.01]. CONCLUSIONS:IgG accumulated in pro-inflammatory M1 macrophages via FcγRs in atherosclerotic lesions. Thus, the target biomolecule-independent imaging of active inflammation should be taken into account in the diagnosis of atherosclerosis using IgG-based probes.
journal_name
Mol Imaging Bioljournal_title
Molecular imaging and biologyauthors
Shimizu Y,Hanzawa H,Zhao Y,Fukura S,Nishijima KI,Sakamoto T,Zhao S,Tamaki N,Ogawa M,Kuge Ydoi
10.1007/s11307-016-1036-8subject
Has Abstractpub_date
2017-08-01 00:00:00pages
531-539issue
4eissn
1536-1632issn
1860-2002pii
10.1007/s11307-016-1036-8journal_volume
19pub_type
杂志文章abstract:PURPOSE:The mTOR kinase inhibitor AZD8055 inhibits both mTORC1 and mTORC2 leading to disruption of glucose metabolism and proliferation pathways. This study assessed the impact of single and multiple doses of AZD8055 on the uptake of the glucose metabolism marker 2-deoxy-2-[(18) F]fluoro-D-glucose ([(18) F]FDG) and the...
journal_title:Molecular imaging and biology
pub_type: 杂志文章
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更新日期:2014-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11307-015-0844-6
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journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-019-01335-4
更新日期:2019-12-01 00:00:00
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journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-005-0028-x
更新日期:2006-01-01 00:00:00
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更新日期:2013-08-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2019-08-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2011-08-01 00:00:00
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更新日期:2016-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-10-13 00:00:00
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pub_type: 杂志文章
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更新日期:2011-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11307-010-0372-3
更新日期:2011-06-01 00:00:00
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journal_title:Molecular imaging and biology
pub_type: 杂志文章
doi:10.1007/s11307-015-0890-0
更新日期:2016-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2021-01-26 00:00:00
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更新日期:2017-12-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2016-10-01 00:00:00
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更新日期:2020-08-01 00:00:00
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pub_type: 已发布勘误
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更新日期:2020-02-01 00:00:00
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更新日期:2008-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-12-01 00:00:00
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