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(Circulation. 2004;109:2554-2559.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Scintigraphic Imaging of Matrix Metalloproteinase Activity in the Arterial Wall In Vivo

Michael Schäfers, MD^*; Burkhard Riemann, MD^*; Klaus Kopka, PhD; Hans-Jörg Breyholz, PhD; Stefan Wagner, PhD; Klaus P. Schäfers, PhD; Marilyn P. Law, BSc; Otmar Schober, MD; Bodo Levkau, MD

From the Department of Nuclear Medicine (M.S., B.R., K.K., H.-J.B., S.W., K.P.S., M.P.L., O.S.), Hospital of the Westfälische Wilhelms-University, Münster; Institute of Arteriosclerosis Research (M.S.), Westfälische Wilhelms-University, Münster; and Institut für Pathophysiologie (B.L.), Zentrum für Innere Medizin, Universitätsklinikum Essen, Germany.

Correspondence to Michael Schäfers, MD, Department of Nuclear Medicine-Experimental Nuclear Medicine, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany. E-mail schafmi{at}uni-muenster.de

Received November 26, 2003; de novo received March 11, 2004; accepted March 11, 2004.

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.

Key Words: imaging • metalloproteinases • atherosclerosis • nuclear medicine

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