Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction
Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction
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DOI：
10.1172/jci200420352
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发表时间：
2004-06-01
影响因子：
15.9
通讯作者：
Sinusas, AJ
中科院分区：
文献类型：
--
作者：
Meoli, DF;Sadeghi, MM;Sinusas, AJ
无创成像策略对于定义血管生成的时间特征和评估血管生成疗法的疗效至关重要。 αvβ3 整合素在血管生成血管中表达，代表了心肌血管生成成像的潜在新靶点。我们在慢性梗死大鼠模型中，证明了铟-111 标记（In-111 标记）αvβ3 靶向药物在损伤诱导的血管生成区域的定位。使用非特异性对照剂建立了针对血管生成的靶向αvβ3成像剂的特异性。随后在梗死后血管生成的犬模型中证实了这种放射性标记的 αvβ3 靶向药物用于体内成像的潜力。使用 In-111 标记的 αvbeta3 靶向药物进行的连续体内双同位素单光子发射计算机断层扫描 (SPECT) 成像显示，刺激血管生成的灌注不足区域出现局灶性放射性示踪剂摄取。梗塞区域心肌放射性示踪剂的摄取增加了四倍，这与血管生成的组织学证据和αvβ3整合素表达增加有关。因此，可以使用 In-111 标记的 alphavbeta3 靶向药物对心脏中的血管生成进行无创成像。血管生成的无创评估可能对心肌梗死后患者的风险分层具有重要意义。这种方法对于无创追踪治疗性心肌血管生成也可能具有重要的临床实用性。
Noninvasive imaging strategies will be critical for defining the temporal characteristics of angiogenesis and assessing efficacy of angiogenic therapies. The alphavbeta3 integrin is expressed in angiogenic vessels and represents a potential novel target for imaging myocardial angiogenesis. We demonstrated the localization of an indium-111-labeled (In-111-labeled) alphavbeta3-targeted agent in the region of injury-induced angiogenesis in a chronic rat model of infarction. The specificity of the targeted alphavbeta3-imaging agent for angiogenesis was established using a nonspecific control agent. The potential of this radiolabeled alphavbeta3-targeted agent for in vivo imaging was then confirmed in a canine model of postinfarction angiogenesis. Serial in vivo dual-isotope single-photon emission-computed tomographic (SPECT) imaging with the In-111-labeled alphavbeta3-targeted agent demonstrated focal radiotracer uptake in hypoperfused regions where angiogenesis was stimulated. There was a fourfold increase in myocardial radiotracer uptake in the infarct region associated with histological evidence of angiogenesis and increased expression of the alphavbeta3 integrin. Thus, angiogenesis in the heart can be imaged noninvasively with an In-111-labeled alphavbeta3-targeted agent. The noninvasive evaluation of angiogenesis may have important implications for risk stratification of patients following myocardial infarction. This approach may also have significant clinical utility for noninvasively tracking therapeutic myocardial angiogenesis.