Uptake of inflammatory cell marker [11C]PK11195 into mouse atherosclerotic plaques
Uptake of inflammatory cell marker [11C]PK11195 into mouse atherosclerotic plaques
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DOI：
10.1007/s00259-008-0919-6
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发表时间：
2009-01-01
影响因子：
9.1
通讯作者：
Knuuti, Juhani
中科院分区：
文献类型：
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作者：
Laitinen, Iina;Marjamaki, Paivi;Knuuti, Juhani
目的[C-11] PK 11195与巨噬细胞中大量表达的外周苯二氮卓类受体（benzodiazepine receptor，PBR）具有高亲和力和选择性结合。在人体中，[C-11] PK 11195已成功用于脑组织炎症过程的体内成像。本研究的目的是探讨[C-11] PK 11195在动脉粥样硬化斑块炎症成像中的可行性。方法通过检测[H-3] PK 11195与小鼠主动脉切片的体外结合来验证动脉粥样硬化斑块中存在PK 11195结合位点。在LDLR/ApoB 48动脉粥样硬化小鼠的切除组织样本和主动脉切片中离体研究静脉给药[C-11] PK 11195的摄取。结果[H-3] PK 11195可与动脉粥样硬化斑块和健康血管壁结合，并可与正常血管壁结合。放射自显影分析显示，[C-11] PK 11195在斑块中炎症区域的摄取比非炎症斑块区域更显著（p=0.011），但总体上不高于健康血管壁的摄取。此外，11 C放射性的积累到动脉粥样硬化小鼠的主动脉没有增加相比，健康对照mice.Conclusions我们的研究结果表明，[C-11] PK 11195的摄取是在炎症动脉粥样硬化斑块含有大量的炎性细胞比在非炎症斑块。然而，动脉壁其他结构的示踪剂摄取也很突出，可能限制[C-11] PK 11195在动脉粥样硬化斑块临床成像中的使用。
Purpose The ligand [C-11]PK11195 binds with high affinity and selectivity to peripheral benzodiazepine receptor, expressed in high amounts in macrophages. In humans, [C-11] PK11195 has been used successfully for the in vivo imaging of inflammatory processes of brain tissue. The purpose of this study was to explore the feasibility of [C-11] PK11195 in imaging inflammation in the atherosclerotic plaques.Methods The presence of PK11195 binding sites in the atherosclerotic plaques was verified by examining the in vitro binding of [H-3] PK11195 onto mouse aortic sections. Uptake of intravenously administered [C-11] PK11195 was studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48 atherosclerotic mice. Accumulation of the tracer was compared between the atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography and histological analyses.Results The [H-3] PK11195 was found to bind to both the atherosclerotic plaques and the healthy wall. The autoradiography analysis revealed that the uptake of [C-11] PK11195 to inflamed regions in plaques was more prominent (p=0.011) than to non-inflamed plaque regions, but overall it was not higher than the uptake to the healthy vessel wall. Also, the accumulation of 11C radioactivity into the aorta of the atherosclerotic mice was not increased compared to the healthy control mice.Conclusions Our results indicate that the uptake of [C-11] PK11195 is higher in inflamed atherosclerotic plaques containing a large number of inflammatory cells than in the non-inflamed plaques. However, the tracer uptake to other structures of the artery wall was also prominent and may limit the use of [C-11] PK11195 in clinical imaging of atherosclerotic plaques.