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Introduction:Abdominal Aortic Aneurysm (AAA) development is common in the aging population, and AAA rupture carries a high mortality. AAA development is characterized by destructive extracellular matrix remodeling by mononuclear phagocytes. Monocyte chemoattractant protein/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, by positron emission tomography (PET) imaging, is predictive of subsequent rupture. We also sought to determine if CCR2 inhibition can prevent AAA rupture.Methods:Forty-three male Sprague-Dawley rats underwent intraluminal aortic exposure to porcine pancreatic elastase (PPE) to induce aneurysmal degeneration. Four groups were considered: 1. Active PPE (AAA), 2. Heat-inactivated PPE (Control), 3. APPE + ?-aminopropionitrile (BAPN), a lysyl oxidase inhibitor to stimulate AAA rupture (RAAA), and 4. APPE + BAPN + RS-504393, a CCR2 inhibitor (TxAAA). 64Cu-DOTA-ECL1i PET imaging was performed 7 and 14 days post AAA induction.Results:AAAs demonstrated significantly greater 64Cu-DOTA-ECL1i uptake by PET imaging compared to controls (p<0.05), and this was confirmed by autoradiography. RAAAs that subsequently ruptured demonstrated significantly greater 64Cu-DOTA-ECL1i uptake compared to those that did not (p<0.001 ). RAAAs ruptured at a rate of 49%, with a mean aortic diameter increase of 345 % ? 35 %, while TxAAAs did not generate aneurysms and ruptured at a rate of 20%, with a mean aortic diameter increase of 85 % ? 6 % (p<0.0001). As an additional marker of macrophage presence, TxAAA MMP9 activity by zymography was significantly lower than that of AAAs and RAAAs that did not rupture (p<0.05).Conclusions:CCR2 targeted PET imaging demonstrated inflammation associated with rat AAA development. Increased radiotracer uptake by AAAs that subsequently rupture warrants further study to determine the ability of 64Cu-DOTA-ECL1i PET imaging to aid in assessing AAA rupture potential. CCR2 inhibition with our model decreases AAA development and prevents AAA rupture, suggesting a theranostic role for CCR2 in the treatment of AAA patients.