S. Elizondo Benedetto1, R. Wahidi1, M. Hamdi2, M. Zaghloul1, S. Hafezi1, B. Arif1, G.S. Heo2, D. Sultan2, H. Luehmann2, L. Detering2, J. Ippolito2, J. Zheng2, R. Laforest2, R.J. Gropler2, Y. Liu2, L. Sanchez1, N.M. Droz1, B.G. Rubin1, J.W. Ohman1, Z.J. Wanken1, L. McDonald1, M.A. Zayed1,2,3,4,5,6 1Washington University, Vascular Surgery, St. Louis, MO, USA 2Washington University, Radiology, St. Louis, MO, USA 3Washington University, Molecular Cell Biology, St. Louis, MO, USA 4Washington University, Surgical Sciences, St. Louis, MO, USA 5Washington University, Biomedical Engineering, St. Louis, MO, USA 6Saint Louis Veterans Affairs Medical Center, Saint Louis, MO, USA
Introduction: Abdominal aortic aneurysm (AAA) risk stratification is an unmet clinical need since they often remain asymptomatic until they acutely rupture. Traditional imaging focuses predominantly on AAA diameter and growth rate, which neglects key cellular and molecular processes associated with aneurysm expansion and the risk of rupture. Pre-clinical studies suggest that high CCR2 (C-C chemokine receptor 2) PET signal, is predictive of AAA rupture. We hypothesized that CCR2-targeted PET radiotracer can be used as a reliable diagnostic modality for evaluating human AAA wall stress and the risk of rupture.
Methods: In a prospective case-control study, 10 patients with AAA (surgical and non-surgical) and 9 non-AAA controls underwent PET/CT using 64Cu-DOTA-ECL1i. Mean and max standardized uptake value differential (SUVdiff) were calculated at various anatomical locations, such as the highest and lowest renal artery (HRA & LRA), maximum AAA sac (MAS) and mid-infrarenal aorta (MIRA). At each location, specific segments were evaluated: aortic wall, peri-aortic and intraluminal thrombus (ILT) and quadrant sectoring of the aortic wall. Areas of higher mechanical stress in the aorta was determined by rupture predictive index(RPI) via ‘BioPARR’. Intraoperative AAA specimens were collected during open AAA surgical repair.
Results: AAA patients consisted mostly of elderly (70.7±7.3) male, with a baseline aneurysm diameter of 4.86±0.7cm. Compared to controls, there was a higher prevalence of hyperlipidemia and statin use in AAA patients, while other co-morbidities and medications were similar. The AAA group demonstrated a higher CCR2 PET/CT signal compared to the controls, specifically in areas of established disease (p=0.01 Fig1A-C). Interestingly, the surgical AAA group demonstrated higher CCR2 at the wall of MAS when compared to non-surgical AAAs, despite having similar aortic diameter (Fig1D&E). Histology of surgical AAA samples showed elevated CCR2+ staining (Fig1F). Moreover, a subgroup of AAA patients with the highest CCR2 signal at MAS (p<0.01), also demonstrated the highest signal at the posterior aortic quadrant (p<0.03 Fig1G&I). Similarly, the peak RPI value was found at the posterior quadrant of MAS (p<0.05 Fig1H&J). Furthermore, there was a significantly positive correlation between CCR2 PET signal and RPI (p=0.04 Fig1K).
Conclusion: This first-in-human study demonstrates that CCR2-targeted radiotracer imaging is feasible, and the inflammation identified is associated with risk of mechanical rupture in individuals with AAAs. This molecular diagnostic strategy may provide a new avenue for identifying individuals with AAAs who are at higher risk of disease progression and subsequent rupture.