Assessment Of Abdominal Aortic Aneurysm Inflammation And Rupture Prediction With Ccr2 Pet

23 Objectives: The monocyte chemoattractant protein-1/chemokine receptor 2 (CCR2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. Our goal was to assess the expression of CCR2 in a rodent model and human tissue, utilizing a targeted positron emission tomography (PET) radiotracer (64Cu-DOTA-ECL1i).\n Methods: AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to porcine pancreatic elastase (PPE) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was utilized to generate a sham operative control. Rat AAA rupture was stimulated by the administration of β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of 64Cu-DOTA-ECL1i. The localization of radiotracer uptake in the AAA was verified with high-resolution computed tomography (CT).\n Results: At day 7 post AAA induction, the radiotracer uptake (SUV= 0.91 ± 0.25) was approximately twice that of sham-operated controls (SUV = 0.47 ± 0.10, p \u003c 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 \u003c 0.005) demonstrated uptake nearly twice that of non-ruptured AAAs (SUV = 0.73 ± 0.11). Histopathological 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 and correlation to CCR2 expression.\n Conclusions: CCR2 PET is a promising new biomarker for the non-invasive assessment of AAA inflammation that may aid in associated rupture prediction.\nResearch Support: This work is supported by NIH R35HL145212, P41EB025815, Wylie Scholar Award from Vascular Cures Foundation, the Institute of Clinical and Translational Sciences (ICTS) of Washington University, and Foundation for Barnes-Jewish Hospital.