18F-Fluorodeoxyglucose-Positron Emission Tomography Imaging Detects Response to Therapeutic Intervention and Plaque Vulnerability in a Murine Model of Advanced Atherosclerotic Disease-Brief Report.

Academic Article

Abstract

  • OBJECTIVE: This study sought to determine whether 18F-fluorodeoxyglucose-positron emission tomography/computed tomography could be applied to a murine model of advanced atherosclerotic plaque vulnerability to detect response to therapeutic intervention and changes in lesion stability. Approach and Results: To analyze plaques susceptible to rupture, we fed ApoE-/- mice a high-fat diet and induced vulnerable lesions by cast placement over the carotid artery. After 9 weeks of treatment with orthogonal therapeutic agents (including lipid-lowering and proefferocytic therapies), we assessed vascular inflammation and several features of plaque vulnerability by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography and histopathology, respectively. We observed that 18F-fluorodeoxyglucose-positron emission tomography/computed tomography had the capacity to resolve histopathologically proven changes in plaque stability after treatment. Moreover, mean target-to-background ratios correlated with multiple characteristics of lesion instability, including the corrected vulnerability index. CONCLUSIONS: These results suggest that the application of noninvasive 18F-fluorodeoxyglucose-positron emission tomography/computed tomography to a murine model can allow for the identification of vulnerable atherosclerotic plaques and their response to therapeutic intervention. This approach may prove useful as a drug discovery and prioritization method.
  • Authors

    Keywords

  • atherosclerosis, inflammation, mice, plaque, atherosclerotic, stroke, Animals, Antibodies, Blocking, Atorvastatin, CD47 Antigen, Carotid Artery Diseases, Carotid Artery, Common, Disease Models, Animal, Fluorodeoxyglucose F18, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Mice, Inbred C57BL, Mice, Knockout, ApoE, Plaque, Atherosclerotic, Positron Emission Tomography Computed Tomography, Predictive Value of Tests, Radiopharmaceuticals, Rupture, Spontaneous
  • Digital Object Identifier (doi)

    Author List

  • Jarr K-U; Ye J; Kojima Y; Nanda V; Flores AM; Tsantilas P; Wang Y; Hosseini-Nassab N; Eberhard AV; Lotfi M
  • Start Page

  • 2821
  • End Page

  • 2828
  • Volume

  • 40
  • Issue

  • 12