CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction.
Circ Cardiovasc Imaging
; 13(3): e009889, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-32164451
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 ß-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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aorta Abdominal
/
Regulación de la Expresión Génica
/
Aneurisma de la Aorta Abdominal
/
Aneurisma Roto
/
Tomografía de Emisión de Positrones
/
Receptores CCR2
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Circ Cardiovasc Imaging
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
DIAGNOSTICO POR IMAGEM
Año:
2020
Tipo del documento:
Article
País de afiliación:
Macao