RADIOPHARMACY AND RADIOPHARMACEUTICALS 2007 UPDATE 

The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2007 March;51(1):24-32

Copyright © 2007 EDIZIONI MINERVA MEDICA

language: English

A 18F-radiolabeled analogue of CGS 27023A as a potential agent for assessment of matrix-metalloproteinase activity in vivo

Breyholz H. J. ¹, Wagner S. ¹, Levkau B. ², Schober O. ¹, Schäfers M. ^{1, 3}, Kopka K. ^{1, 3}

¹ Department of Nuclear Medicine University Hospital Münster, Münster, Germany 2 Institute of Pathophysiology, Center of Internal Medicine University Hospital Essen, Essen, Germany 3 Interdisciplinary Center of Clinical Research (IZKF) Münster, Germany

Aim. The non-invasive measurement of activated matrix metalloproteinases (MMPs) in vivo, which are involved in many pathophysiological and pathological processes occurring in inflammation, cancer and atherosclerosis, is a clinical challenge. A diagnostic tool for the non-invasive detection of MMP activity in vivo is based on MMP inhibitor (MMPI) radiotracers.
Methods. We chose non-peptidyl broad-spectrum MMPI CGS 27023A 1 as a hydroxamic acid-based lead structure to design such a tracer.
Results. The radioligand HO-[123I]I-CGS 27023A was able to specifically visualize activated MMPs in vascular lesions of apolipoprotein E-deficient mice in vivo. Based upon this work the radiosynthesis of a fluorinated analogue of the MMP inhibitor CGS 27023A was developed. Its unlabeled counterpart was found to be a potent MMP inhibitor in vitro.
Conclusion. Application of this class of MMP-targeting agents in combination with molecular imaging modalities, such as positron emission tomography, may emerge as a novel clinical diagnostic tool in the management of human diseases with MMP misexpression and/or dysregulation.