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Molecular imaging of activated matrix metalloproteinases in vascular remodeling

Jiasheng Zhang1, Lei Nie, Mahmoud Razavian

  • 1Raymond and Beverly Sackler Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn., USA.

Circulation
|October 22, 2008
PubMed
Abstract

Insights

A novel imaging tracer, RP782, successfully detected matrix metalloproteinase (MMP) activation in injured blood vessels. This tracer tracks vascular remodeling in vivo, offering new insights into disease progression.

Area of Science:

  • Cardiovascular Research
  • Medical Imaging
  • Molecular Biology

Background:

  • Matrix metalloproteinase (MMP) activation is crucial for vascular remodeling processes.
  • RP782 is a new indium (111)In-labeled tracer designed to specifically target activated MMPs.
  • This study investigated the potential of RP782 to detect vascular remodeling induced by injury in living organisms.

Purpose of the Study:

  • To evaluate the efficacy of RP782 microSPECT/CT imaging in detecting injury-induced matrix metalloproteinase (MMP) activation.
  • To assess whether RP782 uptake correlates with the extent of vascular remodeling.
  • To determine if RP782 can serve as a tool for tracking vascular remodeling in vivo.

Main Methods:

  • Vascular injury was induced in the left common carotid artery of apolipoprotein E(-/-) mice.
  • Matrix metalloproteinase activity was assessed using in situ zymography.
  • RP782 tracer was administered intravenously at various time points post-injury, followed by microSPECT/CT imaging and quantitative autoradiography.

Main Results:

  • Carotid artery injury resulted in significant hyperplasia and remodeling over 4 weeks, with increased MMP activity.
  • RP782 imaging revealed focal tracer uptake in the injured carotid artery from 2 to 4 weeks post-injury.
  • RP782 uptake demonstrated high specificity and closely correlated with changes in vessel-wall area.

Conclusions:

  • RP782 microSPECT/CT imaging can effectively detect injury-induced matrix metalloproteinase activation in the vessel wall.
  • RP782 uptake serves as a reliable indicator of the hyperplastic process in vascular remodeling.
  • This imaging approach offers a promising method for in vivo tracking of vascular remodeling.

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