NIH CCR2 AAA Study

"The primary goal is to relate preoperative 64Cu-DOTA-ECL1i AAA uptake with CCR2+ cell activity in AAA tissue collected at the time of open repair. We will image AAA patients pre-operatively and collect tissue at the time of open repair in an attempt to demonstrate ex-vivo tissue corroboration of our imaging findings (n=20, 10 women and 10 men).~Participants with AAA will undergo routine clinical evaluation including ultrasound, CT scan and scheduling of open surgical repair. We will record age and tobacco use. If a renal function blood test has not been performed within the past 90 days, we will draw \~2 teaspoons of blood for a creatinine test. A contrast dye will be used for the CT portion of the PET-CT scan. Those having open surgery, their PET/CT imaging will be within 7-14 of the surgery and if available, collection of discarded aortic tissue at the time of surgery."

We will determine the retention of 64Cu-DOTA-ECL1i in abdominal aorta of non-AAA volunteers (n=10, 5 women and 5 men). This group of participants will have a documented absence of AAA by screening ultrasound that was previously obtained as part of standard care. Both men and women, above the age of 40, with or without active tobacco use will be considered for participation.

The primary objective of this sub-aim is to assess the sensitivity and specificity of 64Cu-DOTA-ECL1i binding to ex vivo to human AAA specimens from the Washington University Vascular Surgery Biobank (VS-BB). We will first perform a histopathological evaluation of human AAA specimens (n=75, including samples from this study) and categorize them based on clinical status (e.g, diameter) and degree of inflammation. We will consider healthy, nonatherosclerotic aorta (n=25) as negative controls, and non-aneurysmal aortas (n=25) from patients that have undergone surgery for aortoiliac occlusive disease as positive controls.

The objective of this sub-aim is to better understand the relationship between the levels of CCR2+ inflammatory cells and the inflammatory and clinical status of AAA, to gain insight into the importance of proinflammatory monocytes/macrophages in the development of AAA disease at the time of elective AAA repair. We will correlate the level of MMP expression and activity, as well as cytokine profiles, of each specimen, with the associated histopathological features. The relationship between 64Cu-DOTA-ECL1i binding and CCR2 expression in tissues with different degrees of disease severity will be evaluated using Pearson or Spearman correlation coefficients. This will allow us to speculate as to how tracer uptake will perform in vivo and what that uptake represents in regard to disease severity.

We will demonstrate consistent 64Cu-DOTAECL1i uptake by performing repeated imaging studies in a separate group of non-surgical AAA patients (n=20, 10 women and 10 men). Completion of this sub-aim will provide support for the use of 64Cu-DOTA-ECL1i PET for evaluating AAA disease in a reliable fashion. These participants will have another PET/CT imaging study performed 10-14 days after the first PET/CT in order to determine the ability to reproduce the uptake results of Cu-64-DOTA-ECL1i. The physician will assess the participant's willingness and eligibility to have a second PET/CT scan.