CCR2 正电子发射断层扫描用于评估腹主动脉瘤炎症和破裂预测。
CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction.
机构信息
Department of Surgery, Section of Vascular Surgery (S.J.E., S.E.S., B.A.), Washington University, St. Louis, MO.
Department of Radiology (L.D., D.S., H.L., G.S.H., X.Z., R.L., J.Z., R.J.G., Y.L.), Washington University, St. Louis, MO.
出版信息
Circ Cardiovasc Imaging. 2020 Mar;13(3):e009889. doi: 10.1161/CIRCIMAGING.119.009889. Epub 2020 Mar 13.
BACKGROUND
The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (Cu-DOTA-ECL1i).
METHODS
AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of β-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer.
RESULTS
Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10; <0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14; <0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68 macrophages. Ex vivo autoradiography demonstrated specific binding of Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues.
CONCLUSIONS
CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.
背景
单核细胞趋化蛋白-1/CCR2（趋化因子受体 2）轴在腹主动脉瘤（AAA）发病机制中发挥重要作用，影响疾病进展和解剖稳定性。我们使用靶向正电子发射断层扫描放射性示踪剂（Cu-DOTA-ECL1i）评估了啮齿动物模型和人体组织中 CCR2 的表达。
方法
通过在压力下将猪胰腺弹性蛋白酶（PPE）暴露于肾下、腔内主动脉来在 Sprague-Dawley 大鼠中产生 AAA，以诱导动脉瘤变性。使用热失活的 PPE 产生假手术对照。通过给予赖氨酸氧化酶抑制剂β-氨基丙腈来刺激大鼠 AAA 破裂。在 Cu-DOTA-ECL1i 尾静脉注射后 1 小时，在野生型大鼠中进行生物分布。在大鼠中进行动态正电子发射断层扫描/计算机断层扫描成像，以确定示踪剂的体内分布。
结果
生物分布显示快速的肾脏清除。AAA 中放射性示踪剂摄取的定位通过高分辨率计算机断层扫描得到证实。在 AAA 诱导后第 7 天，放射性示踪剂摄取（标准化摄取值[SUV]=0.91±0.25）约为假手术对照的两倍（SUV=0.47±0.10；<0.01）。在 AAA 诱导后 14 天，两组的放射性示踪剂摄取均无明显变化（AAA SUV=0.86±0.17 和 sham-control SUV=0.46±0.10），与主动脉直径的变化无关。竞争性 CCR2 受体阻断显著降低 AAA 摄取（SUV=0.42±0.09）。随后破裂的 AAA（SUV=1.31±0.14；<0.005）的摄取量几乎是未破裂 AAA（SUV=0.73±0.11）的两倍。从手术中获得的大鼠和人 AAA 组织的组织病理学特征显示 CCR2 表达增加，与 CD68 巨噬细胞共定位。离体放射性自显影显示 Cu-DOTA-ECL1i 特异性结合大鼠和人主动脉组织中的 CCR2。
结论
CCR2 正电子发射断层扫描是一种很有前途的新的 AAA 炎症无创评估生物标志物，可能有助于相关破裂预测。
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