背景:在过去的十年中,血管生成越来越成为成像和治疗的目标。整联蛋白αvβ3在血管生成期间在细胞中高度表达,因此是成像的有希望的靶标。在这项研究中,我们旨在研究PET示踪剂[68Ga]Ga-RGD作为MI后血管生成的标志物及其预测心脏功能参数的能力。
方法:首先,使用表面等离子体共振(SPR)研究了[68Ga]Ga-RGD与整联蛋白αvβ3之间的实时相互作用。第二,在大鼠模型(MI=68,假手术=36)中,进行了一项动物研究,以研究MI后1周和4周后梗死区[68Ga]Ga-RGD的摄取.最后,使用组织学离体评估[68Ga]Ga-RGD示踪剂的特异性,放射自显影,γ计数和流式细胞术。
结果:SPR显示[68Ga]Ga-RGD对整联蛋白αvβ3具有高亲和力,形成强且稳定的结合。与MI后一周(p<0.001)和四周(p<0.001)的假手术相比,PET/CT显示梗死区域中[68Ga]Ga-RGD的摄取明显更高。一周后[68Ga]Ga-RGD的摄取与四周后的舒张末期体积(r=0.74,p<0.001)和射血分数(r=-0.71,p<0.001)相关。
结论:本研究表明[68Ga]Ga-RGD对整联蛋白αvβ3具有高亲和力,这使得能够评估血管生成和重塑。一周后的[68Ga]Ga-RGD摄取表明[68Ga]Ga-RGD可用作MI后心脏功能参数和心力衰竭可能发展的早期预测因子。这些令人鼓舞的数据支持MI患者的临床翻译和未来使用。
BACKGROUND: Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin αvβ3 is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [68Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters.
METHODS: First, the real-time interaction between [68Ga]Ga-RGD and integrin αvβ3 was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [68Ga]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [68Ga]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry.
RESULTS: SPR showed that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, forming a strong and stable binding. PET/CT showed a significantly higher uptake of [68Ga]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [68Ga]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = - 0.71, p < 0.001) after four weeks.
CONCLUSIONS: This study demonstrates that [68Ga]Ga-RGD has a high affinity for integrin αvβ3, which enables the evaluation of angiogenesis and remodeling. The [68Ga]Ga-RGD uptake after one week indicates that [68Ga]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients.