Su Helen, Gorodny Natalia, Gomez Luis Felipe, Gangadharmath Umesh B, Mu Fanrong, Chen Gang, Walsh Joseph C, Szardenings Katrin, Berman Daniel S, Kolb Hartmuth C, Tamarappoo Balaji K
Siemens Molecular Imaging, 6140 Bristol Parkway, Culver City, CA, USA.
J Nucl Cardiol. 2014 Jun;21(3):553-62. doi: 10.1007/s12350-014-9879-3. Epub 2014 Mar 14.
Rupture of unstable atherosclerotic plaque that leads to stroke and myocardial infarction may be induced by macrophage infiltration and neovessel formation. A tracer that selectively binds to integrin αvβ3 a protein expressed by macrophages and neovascular endothelium may identify rupture prone plaque.
(18)F-labeled "R-G-D" containing tripeptide (Flotegatide), a click chemistry derived radiotracer that binds to integrin αvβ3 was injected in ApoE knockout mice fed a high fat diet. Uptake of Flotegatide by atherosclerotic plaque was visualized by micro-PET, autoradiography, and correlated to histologic markers of inflammation and angiogenesis.
We found that Flotegatide preferentially binds to aortic plaque in an ApoE knockout mouse model of atherosclerosis. The tracer's uptake is strongly associated with presence of histologic markers for macrophage infiltration and integrin expression. There is a weaker but detectable association between Flotegatide uptake and presence of an immunohistochemical marker for neovascularization.
We hypothesize that Flotegatide may be a useful tracer for visualization of inflamed plaque in clinical subjects with atherosclerosis and may have potential for detecting vulnerable plaque.
不稳定动脉粥样硬化斑块破裂可导致中风和心肌梗死，其可能由巨噬细胞浸润和新血管形成引发。一种能选择性结合整合素αvβ3（一种由巨噬细胞和新生血管内皮细胞表达的蛋白质）的示踪剂，或许能够识别易破裂斑块。
将含有三肽（弗洛替肽）的（18）F标记的“R - G - D”（一种通过点击化学法得到的与整合素αvβ3结合的放射性示踪剂）注射到喂食高脂肪饮食的载脂蛋白E基因敲除小鼠体内。通过微型正电子发射断层扫描（micro - PET）、放射自显影观察弗洛替肽在动脉粥样硬化斑块中的摄取情况，并将其与炎症和血管生成的组织学标志物相关联。
我们发现，在动脉粥样硬化的载脂蛋白E基因敲除小鼠模型中，弗洛替肽优先与主动脉斑块结合。该示踪剂的摄取与巨噬细胞浸润和整合素表达的组织学标志物的存在密切相关。弗洛替肽摄取与新血管形成的免疫组化标志物的存在之间存在较弱但可检测到的关联。
我们推测，弗洛替肽可能是一种用于可视化临床动脉粥样硬化患者炎症斑块的有用示踪剂，并且可能具有检测易损斑块的潜力。
