CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction.

Abstract

BACKGROUND:

The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (64Cu-DOTA-ECL1i).

METHODS:

AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of β-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of 64Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer.

RESULTS:

Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10; P<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14; P<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68+ macrophages. Ex vivo autoradiography demonstrated specific binding of 64Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues.

CONCLUSIONS:

CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.

• Authors: Sean J English, Sergio E Sastriques, Lisa Detering, Deborah Sultan, Hannah Luehmann, Batool Arif, Gyu Seong Heo, Xiaohui Zhang, Richard Laforest, Jie Zheng, Chieh-Yu Lin, Robert J Gropler, Yongjian Liu
• Journal: Circulation. Cardiovascular imaging (Circ Cardiovasc Imaging) Vol. 13 Issue 3 Pg. e009889 (03 2020) ISSN: 1942-0080 [Electronic] United States
• PMID: 32164451 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers
• Ccr2 protein, rat
• Radiopharmaceuticals
• Receptors, CCR2
• Fluorodeoxyglucose F18
• RNA

Topics

• Aneurysm, Ruptured (diagnosis, genetics, metabolism)
• Animals
• Aorta, Abdominal (diagnostic imaging, metabolism)
• Aortic Aneurysm, Abdominal (diagnosis, genetics, metabolism)
• Biomarkers (metabolism)
• Fluorodeoxyglucose F18 (pharmacology)
• Gene Expression Regulation
• Male
• Positron-Emission Tomography (methods)
• Prognosis
• RNA (genetics)
• Radiopharmaceuticals (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, CCR2 (biosynthesis, genetics)