Scintigraphic imaging of matrix metalloproteinase activity in the arterial wall in vivo

Circulation. 2004 Jun 1;109(21):2554-9. doi: 10.1161/01.CIR.0000129088.49276.83. Epub 2004 May 3.

Abstract

Background: Matrix metalloproteinases (MMPs) are enzymes involved in the proteolytic degradation of extracellular matrix. They play an important role in several disease processes, such as inflammation, cancer, and atherosclerosis.

Methods and results: In this study, we have used the broad-spectrum MMP inhibitor CGS 27023A to develop the radioligand [123I]I-HO-CGS 27023A for in vivo imaging of MMP activity. Using this radioligand, we were able to specifically image MMP activity by scintigraphy in vivo in the MMP-rich vascular lesions that develop after carotid artery ligation and cholesterol-rich diet in apolipoprotein E-deficient mice. These results were confirmed by gamma counting of lesional tissue (counts per minute per milligram).

Conclusions: Imaging of MMP activity in vivo is feasible using radiolabeled MMP inhibitors. Additional studies are needed to test the potential of this approach as a novel noninvasive clinical diagnostic tool for the management of human MMP-related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Autoradiography
  • Carotid Artery, Common / diagnostic imaging
  • Carotid Artery, Common / enzymology*
  • Carotid Artery, Common / pathology
  • Diet, Atherogenic
  • Feasibility Studies
  • Hydroxamic Acids / pharmacology
  • Iodine Radioisotopes
  • Ligation
  • Macrophages / pathology
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase Inhibitors*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protease Inhibitors / pharmacology
  • Pyrazines / pharmacology
  • Radionuclide Imaging
  • Radiopharmaceuticals
  • Sulfonamides / pharmacology

Substances

  • Apolipoproteins E
  • CGS 27023A
  • Hydroxamic Acids
  • Iodine Radioisotopes
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Pyrazines
  • Radiopharmaceuticals
  • Sulfonamides
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9