Pilot first-in-human CCR2 PET/CT to detect abdominal aortic aneurysm wall instability

Objective: In a pilot first-in-human study, we aimed to evaluate the feasibility of Positron Emission Tomography/Computed Tomography (PET/CT) imaging of C-C chemokine receptor type 2 (CCR2) to aid in the diagnosis of abdominal aortic aneurysm (AAA) instability. Rationale: Risk stratification of AAAs is an unmet clinical need. Patients often remain asymptomatic until they acutely rupture. Current imaging techniques focus on AAA diameter and growth rate, neglecting key cellular and molecular processes. Methods: A pilot, prospective, single-center, case-control study evaluated patients with and without AAAs. The study subjects received intravenous administration of a CCR2-specific radiotracer, followed by PET/CT assessment. Surgical AAA specimens were collected to evaluate CCR2 content and extracellular matrix integrity. PET/CT signals were evaluated in the AAA wall in the para-renal, mid-infrarenal, and aneurysm sac, and analyzed relative to patient demographics, AAA anatomical segmentation, and wall rupture potential index (RPI). Results: The AAA group was elderly (70.7 ± 7.3), with an aneurysm diameter of 4.86 ± 0.75 cm, and a higher prevalence of hyperlipidemia and statin use. Regardless of the anatomical segment analyzed, AAA surgical patients demonstrated a higher CCR2 radiotracer signal in the aortic tissue than others. However, no correlation was observed between the radiotracer signal and the AAA diameter. Patients with a higher radiotracer signal, particularly in the AAA posterior wall of the maximum-diameter region, were significantly correlated with RPI (P = 0.03). Histomorphic analysis demonstrated significantly elevated CCR2 levels, along with increased macrophage infiltration, matrix metalloproteinase activity, and severe elastin degradation. Conclusions: This first-in-human study demonstrated that CCR2 PET/CT molecular imaging is feasible and can identify increased wall instability in individuals with AAAs, especially in those at higher risk of disease progression.