A 18F-radiolabeled analogue of CGS 27023A as a potential agent for assessment of matrix-metalloproteinase activity in vivo.
OBJECTIVE
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-[(123)I]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.


CONCLUSIONS
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.
Breyholz
H J
HJ
Department of Nuclear Medicine, University Hospital Münster, Münster, Germany. breyholz@uni-muenster.de
Wagner
S
S
Levkau
B
B
Schober
O
O
Schäfers
M
M
Kopka
K
K
D016503:Drug Delivery Systems / Q000379:methods; D004789:Enzyme Activation; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D006877:Hydroxamic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000378:metabolism; D011719:Pyrazines / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics
C097658:CGS 27023A; D005462:Fluorine Radioisotopes; D006877:Hydroxamic Acids; D011719:Pyrazines; D019275:Radiopharmaceuticals; D013449:Sulfonamides; D020782:Matrix Metalloproteinases