CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction.
Aneurysm, Ruptured
/ diagnosis
Animals
Aorta, Abdominal
/ diagnostic imaging
Aortic Aneurysm, Abdominal
/ diagnosis
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
abdominal aortic aneurysm
autoradiography
cc chemokine receptor 2
molecular imaging
positron emission tomography
rupture
Journal
Circulation. Cardiovascular imaging
ISSN: 1942-0080
Titre abrégé: Circ Cardiovasc Imaging
Pays: United States
ID NLM: 101479935
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
entrez:
14
3
2020
pubmed:
14
3
2020
medline:
20
8
2020
Statut:
ppublish
Résumé
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 ( 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 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; CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.
Sections du résumé
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 (
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
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;
CONCLUSIONS
CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.
Identifiants
pubmed: 32164451
doi: 10.1161/CIRCIMAGING.119.009889
pmc: PMC7101060
mid: NIHMS1563628
doi:
Substances chimiques
Biomarkers
0
Ccr2 protein, rat
0
Radiopharmaceuticals
0
Receptors, CCR2
0
Fluorodeoxyglucose F18
0Z5B2CJX4D
RNA
63231-63-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e009889Subventions
Organisme : NHLBI NIH HHS
ID : R35 HL145212
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB025815
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL131908
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025097
Pays : United States
Organisme : NIH HHS
ID : S10 OD021629
Pays : United States
Commentaires et corrections
Type : CommentIn
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