Synthesis and preliminary biological evaluation of new radioiodinated MMP inhibitors for imaging MMP activity in vivo

Kopka, Klaus; Breyholz, Hans-Jörg; Wagner, Stefan; Law, Marilyn P.; Riemann, Burkhard; Schröer, Sandra; Trub, Monika; Guilbert, Bénédicte; Levkau, Bodo; Schober, Otmar; Schäfers, Michael

doi:10.1016/j.nucmedbio.2003.08.003

Cited by 68 publications

(62 citation statements)

References 25 publications

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“…As with many imaging agents, the proof of principle of imaging of MMPs was obtained in tumors. [81][82][83][84][85][86][87] Substantial studies with MMP imaging have been undertaken in the imaging of atherosclerotic plaques wherein the MMPs have been implicated in plaque instability and fibrous cap thinning. Schäfers et al reported the feasibility of MMP imaging using 123 I-labeled broad-spectrum MMP inhibitor (CGS 27023A) in a carotid ligation model of atherosclerosis in ApoE −/− mice.…”

Section: Imaging Matrix-degrading Enzymesmentioning

confidence: 99%

Molecular Imaging of the Cardiac Extracellular Matrix

Haas

Arbustini

Fuster

et al. 2014

Circulation Research

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Section: Imaging Matrix-degrading Enzymesmentioning

confidence: 99%

Molecular Imaging of the Cardiac Extracellular Matrix

Haas

Arbustini

Fuster

et al. 2014

Circulation Research

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“…One of the key molecular components of the invasive behaviour is the production of MMPs. PET tracers of MMP activity are currently being developed using 125 I-and 18 Flabelled analogues of the non-peptidyl broad-spectrum MMP inhibitor CGS 27023A [87,88]. Animal studies suggest this preferentially detects activity of MMP-1, -2 and -9 [87], the MMPs with the most important activity in gliomas [89].…”

Section: Imaging Biomarkers Of Tumour Invasionmentioning

confidence: 99%

Imaging biomarkers of brain tumour margin and tumour invasion

Price

Gillard²

2011

BJR

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ABSTRACT. Invasion of tumour cells into the normal brain is one of the major reasons of treatment failure for gliomas. Although there is a good understanding of the molecular and cellular processes that occur during this invasion, it is not possible to detect the extent of the tumour with conventional imaging. However, there is an understanding that the degree of invasion differs with individual tumours, and yet they are all treated the same. Newer imaging techniques that probe the pathological changes within tumours may be suitable biomarkers for invasion. Imaging methods are now available that can detect subtle changes in white matter organisation (diffusion tensor imaging), tumour metabolism and cellular proliferation (using MR spectroscopy and positron emission tomography) occurring in regions of tumour that cannot be detected by conventional imaging. The role of such biomarkers of invasion should allow better delineation of tumour margins, which should improve treatment planning (especially surgery and radiotherapy) and provide information on the invasiveness of an individual tumour to help select the most appropriate therapy and help stratify patients for clinical trials.

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“…The broad-spectrum MMP inhibitor CGS 27023A ( Figure 1a) was synthesized de novo, as recently described, 9 and modified for labeling with [ ]iodine; the methoxy moiety of the lead compound CGS 27023A was substituted with the hydroxy group as previously published. 6 This compound was then radioiodinated by a slightly modified standard procedure, 7 125 I]I-HO-CGS 27023A (specific activity, 0.2 GBq/g), respectively.…”

Section: Synthesis Of [ 123 I/ 125 I]i-ho-cgs 27023amentioning

confidence: 99%

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

et al. 2004

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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 [ 123 I]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.

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Synthesis and preliminary biological evaluation of new radioiodinated MMP inhibitors for imaging MMP activity in vivo

Cited by 68 publications

References 25 publications

Molecular Imaging of the Cardiac Extracellular Matrix

Molecular Imaging of the Cardiac Extracellular Matrix

Imaging biomarkers of brain tumour margin and tumour invasion

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

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