Evaluation of CCR2 as a theranostic biomarker for abdominal aortic aneurysm

133 Objectives: Abdominal aortic aneurysms (AAA) represent a life-threatening degenerative vascular disease without any medical therapy. Previously, we have reported that chemokine receptor 2 (CCR2) as a promising target for AAA diagnosis and rupture prediction. Herein, our goal was to evaluate CCR2 as a theranostic biomarker following CCR2 inhibitor treatment. Moreover, we have also assessed the performance of CCR2-targeted PET tracer imaging AAA patients. Methods: A surgical AAA induction model in Sprague-Dawley rats utilizing intra-aortic exposure to porcine pancreatic elastase (PPE) under pressure was used to study the treatment response. The rat AAA rupture (RAAA) model was generated by the administration of β-aminopropionitrile (BAPN) to a AAA rat model. A CCR2 antagonist, RS504393, was selected to inhibit AAA expansion and rupture and administrated via oral gavage at day 0 post AAA induction. Dynamic CCR2 PET/CT scans were performed at 45-60 min post tail vein injection of CCR2 binding tracer 64Cu-DOTA-ECL1i. The CCR2-targeted PET imaging of AAA patients has been carried out under eIND 137620. Results: Following RS504393 treatment, the AAA rupture rate was significantly decreased by 3-fold from 49% (17/35) to 15% (2/13) at day 6 post inhibition. The maximum aortic diameter of RS504393-treated group was also 3-fold less (p Conclusions: CCR2 is a promising theranostic biomarker for PET imaging and a targeted therapy to manage AAA. The early-phase clinical studies of 64Cu-DOTA-ECL1i confirm its safety and demonstrate its potential for CCR2 imaging in AAA patients with PET/CT. Research Support: This work is supported by NIH R35HL145212, R01HL153436, 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.