S. E. Sastriques Dunlop1, S. J. English1 1Washington University,Surgery,St. Louis, MO, USA
Introduction: Abdominal aortic aneurysm (AAA) development is common in the aging population, and AAA rupture is associated with high mortality. Indications for surgical intervention and AAA rupture prediction rely on antiquated aortic diameter criteria. AAA development is characterized by destructive remodeling of the aortic extra cellular matrix, in part by mononuclear phagocytes. Previous work suggests that the monocyte chemoattractant protein (MCP-1)/C-C chemokine receptor type 2 (CCR2) axis plays an important role in AAA development. We sought to evaluate if increased rat AAA uptake of 64Cu-DOTA-ECL1i, a radiolabeled CCR2 binding peptide under current clinical evaluation, by positron emission tomography (PET) imaging, is predictive of subsequent AAA rupture.
Methods: ECL1i was conjugated to a DOTA chelator and radiolabeled with 64Cu. 64Cu-DOTA-ECL1i biodistribution analysis was performed in male Sprague-Dawley (SD) rats (N = 4). Utilizing the porcine pancreatic elastase (PPE) exposure model, infrarenal abdominal aortas of male SD rats were exposed to active PPE to induce AAA formation, and each animal received b-aminopropionitrile (BAPN, N = 8) to stimulate AAA rupture. PET imaging was performed at 6 days post AAA induction, and AAA uptake was quantified by mean standardized uptake values (SUVmean). AAA radiotracer uptake was confirmed by ex vivo autoradiography after PET imaging. Immunohistochemistry and RT-PCR were also utilized to identify CCR2 in AAA tissue.
Results: Biodistribution analysis demonstrated rapid renal clearance of 64Cu-DOTA-ECL1i, with less than 0.5% ID/g in blood 1 hour post intravenous via tail vein injection. PET imaging demonstrated tracer uptake by AAAs that subsequently ruptured (RAAA, N = 5), as well as those AAAs that did not rupture (NRAAA, N = 3). See Figure. RAAAs demonstrated greater 64Cu-DOTA-ECL1i uptake (SUVmean 0.75±0.05) than NRAAAs (SUV mean 0.67 ± 0.05) (p = 0.07). Ex vivo autoradiography confirmed 64Cu-DOTA-ECL1i uptake in each case; while immunohistochemistry and RT-PCR demonstrated upregulation of the CCR2 receptor in each case as well.
Conclusion: CCR2 targeted 64Cu-DOTA-ECL1i PET imaging demonstrated inflammation associated with rat AAA development. Increased radiotracer uptake by AAAs that subsequently ruptured warrants further study to determine the ability of 64Cu-DOTA-ECL1i PET imaging to aid in assessing AAA rupture potential associated with our model, as well as for patients.
