使用靶向整合素 α(v)β3 的示踪剂 99mTc-RAFT-RGD 进行心肌血管生成的体内分子成像。
In vivo molecular imaging of myocardial angiogenesis using the alpha(v)beta3 integrin-targeted tracer 99mTc-RAFT-RGD.
机构信息
INSERM U877, Radiopharmaceutiques Biocliniques, Faculté de Médecine de Grenoble, 38700 La Tronche, Grenoble, France.
出版信息
J Nucl Cardiol. 2010 Jun;17(3):435-43. doi: 10.1007/s12350-010-9191-9. Epub 2010 Jan 20.
BACKGROUND
Myocardial angiogenesis following reperfusion of an infarcted area may impact on patient prognosis and pro-angiogenic treatments are currently evaluated. The non-invasive imaging of angiogenesis would therefore be of potential clinical relevance in these settings. (99m)Tc-RAFT-RGD is a novel (99m)Tc-labeled tracer that targets the alpha(v)beta(3) integrin. Our objective was to determine whether this tracer was suitable for myocardial angiogenesis imaging.
METHODS AND RESULTS
A rat model of reperfused myocardial infarction was employed. Fourteen days following reperfusion, the animals were injected with (99m)Tc-RAFT-RGD or with its negative control (99m)Tc-RAFT-RAD. Fourteen animals were dedicated to autoradiographic imaging, infarct staining, and gamma-well counting of myocardial activity. In vivo dual-isotope pinhole SPECT imaging of (201)Tl and (99m)Tc-RAFT-RGD or (99m)Tc-RAFT-RAD was also performed in 11 additional animals. Neovessels were observed by immunostaining in the infarcted and peri-infarct areas. (99m)Tc-RAFT-RGD infarct-to-normal ratios by gamma-well counting and ex vivo imaging (2.5 +/- 0.6 and 4.9 +/- 0.9, respectively) were significantly higher than those of (99m)Tc-RAFT-RAD (1.7 +/- 0.2 and 2.2 +/- 0.4, respectively, P < .05). The infarcted area was readily visible in vivo by SPECT with (99m)Tc-RAFT-RGD but not with (99m)Tc-RAFT-RAD (infarct-to-normal zone activity ratio, 2.5 +/- 0.6 and 1.7 +/- 0.4, respectively, P < .05).
CONCLUSION
(99m)Tc-RAFT-RGD allowed the experimental in vivo molecular imaging of myocardial angiogenesis.
背景
梗死区再灌注后心肌血管生成可能影响患者预后，目前正在评估促血管生成治疗。因此，在这些情况下，血管生成的非侵入性成像可能具有潜在的临床相关性。(99m)Tc-RAFT-RGD 是一种新型的（99m)Tc 标记示踪剂，靶向 alpha(v)beta(3)整合素。我们的目的是确定这种示踪剂是否适合心肌血管生成成像。
方法和结果
采用大鼠再灌注心肌梗死模型。再灌注后 14 天，动物注射（99m)Tc-RAFT-RGD 或其阴性对照（99m)Tc-RAFT-RAD。14 只动物专门用于放射性自显影、梗死染色和心肌活性的伽马井计数。另外 11 只动物还进行了（201)Tl 和（99m)Tc-RAFT-RGD 或（99m)Tc-RAFT-RAD 的双同位素微孔 SPECT 成像。免疫染色观察到梗死区和梗死周边区的新生血管。（99m)Tc-RAFT-RGD 伽马井计数和离体成像的梗死与正常比值（分别为 2.5+/-0.6 和 4.9+/-0.9）明显高于（99m)Tc-RAFT-RAD（分别为 1.7+/-0.2 和 2.2+/-0.4，P<0.05）。（99m)Tc-RAFT-RGD 可在体内 SPECT 中清晰显示梗死区，但（99m)Tc-RAFT-RAD 则不行（梗死与正常区活性比值，分别为 2.5+/-0.6 和 1.7+/-0.4，P<0.05）。
结论
（99m)Tc-RAFT-RGD 允许心肌血管生成的实验性体内分子成像。
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