Bentsen Simon, Clemmensen Andreas, Loft Mathias, Flethøj Mette, Debes Karina Poulsdóttir, Ludvigsen Trine Pagh, Larsen Cecilie Bjørstrup, Kirchhoff Jeppe, Olsen Lisbeth Høier, Møller Jacob Eifer, Andersen Thomas Lund, Johannesen Helle Hjorth, Jespersen Thomas, Kjaer Andreas
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, DK-2100 Copenhagen, Denmark.
Global Drug Discovery, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
Diagnostics (Basel). 2021 Sep 30;11(10):1807. doi: 10.3390/diagnostics11101807.
Angiogenesis is crucial in tissue repair and prevents scar tissue formation following an ischemic event such as myocardial infarction. The ischemia induces formation of new capillaries, which have high expression of integrin αβ. [Ga]Ga-NODAGA-E[(cRGDyK)] ([Ga]Ga-RGD) is a promising PET-radiotracer reflecting angiogenesis by binding to integrin αβ. A Göttingen mini-pig underwent transient catheter-induced left anterior descending artery (LAD) occlusion for 120 min, and after 8 weeks was imaged on a Siemens mMR 3T PET/MR system. A large antero-septal infarction was evident by late gadolinium enhancement (LGE) on the short axis and 2-4 chamber views. The infarcted area corresponded to the area with high [Ga]Ga-RGD uptake on the fused PET/MR images, with no uptake in the healthy myocardium. To support the hypothesis that [Ga]Ga-RGD uptake reflects angiogenesis, biopsies were sampled from the infarct border and healthy myocardium. Expression of αβ was evaluated using immunohistochemistry. The staining showed higher αβ expression in the capillaries of the infarct border compared to those in the healthy myocardium. These initial data confirm in vivo detection of angiogenesis using [Ga]Ga-RGD PET in a translational model, which overall support the method applicability when evaluating novel cardio-protective therapies.
血管生成在组织修复中至关重要，并可防止在诸如心肌梗死等缺血事件后形成瘢痕组织。缺血诱导新毛细血管形成，这些新毛细血管整合素αβ表达较高。[镓]镓-氮杂环十二烷四乙酸-依[(环肽cRGDyK)]（[镓]镓-环肽）是一种很有前景的正电子发射断层显像（PET）放射性示踪剂，通过与整合素αβ结合来反映血管生成。一只哥廷根小型猪接受经导管短暂性左前降支动脉（LAD）闭塞120分钟，8周后在西门子mMR 3T PET/MR系统上进行成像。在短轴和两腔及四腔视图上，延迟钆增强（LGE）显示出明显的大面积前间隔梗死。梗死区域与融合PET/MR图像上[镓]镓-环肽摄取高的区域相对应，健康心肌无摄取。为支持[镓]镓-环肽摄取反映血管生成这一假说，从梗死边界和健康心肌处采集活检样本。使用免疫组织化学评估αβ的表达。染色显示，与健康心肌中的毛细血管相比，梗死边界处的毛细血管αβ表达更高。这些初步数据证实在一个转化模型中使用[镓]镓-环肽PET对血管生成进行了体内检测，总体上支持了该方法在评估新型心脏保护疗法时的适用性。
