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 (⁶⁴Cu-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 ⁶⁴Cu-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; P<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; P<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 ⁶⁴Cu-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.

中文翻译：

---

CCR2正电子发射断层显像技术，用于评估腹主动脉瘤炎症和破裂预测。

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）发病机理中起重要作用，对疾病的进展和解剖学稳定性有影响。我们使用靶向正电子发射断层显像示踪剂（⁶⁴ Cu-DOTA-ECL1i）评估了CCR2在啮齿动物模型和人体组织中的表达。方法：通过将肾下，管腔内主动脉暴露于PPE（Sprague-Dawley大鼠）产生AAAs（猪胰弹性蛋白酶）在压力下诱发动脉瘤变性。使用热灭活的PPE产生假手术对照。通过给予赖氨酰氧化酶抑制剂β-氨基丙腈刺激大鼠AAA破裂。在尾静脉注射后1小时，在野生型大鼠中进行生物分布。⁶⁴ Cu-DOTA-ECL1i。对大鼠进行动态正电子发射断层扫描/计算机断层扫描成像，以确定放射性示踪剂的体内分布。结果：生物分布显示肾脏清除率快。高分辨率计算机断层扫描验证了AAA中放射性示踪剂摄取的定位。在AAA诱导后第7天，放射性示踪剂的摄取（标准摄取值[SUV] = 0.91±0.25）大约是假对照（SUV = 0.47±0.10；P）的两倍。<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和假对照SUV = 0.46±0.10），而与主动脉直径的变化无关。竞争性CCR2受体阻滞显着降低AAA吸收（SUV = 0.42±0.09）。随后破裂的AAA中的示踪剂摄取（SUV = 1.31±0.14; P <0.005）显示其摄取量几乎是未破裂的AAA的示踪剂摄取（SUV = 0.73±0.11）。通过手术获得的大鼠和人类AAA组织的组织病理学特征显示与CD68 ⁺巨噬细胞共定位的CCR2表达增加。体外放射自显影显示特异性结合⁶⁴结论：CCR2正电子发射断层扫描是一种无创评估AAA炎症的新的生物标志物，可能有助于相关的破裂预测。CC-DOTA-ECL1i在大鼠和人主动脉组织中均具有CCR2作用。