AI Article Synopsis
- Excess matrix degradation is key in cancer progression, impacting various processes like invasion and metastasis, making matrix metalloproteinases (MMPs) important targets for therapy and diagnostics.
- MMP expression is higher near tumors, allowing for targeted medical imaging; researchers synthesized radioiodinated MMP inhibitors and achieved good radiochemical yields.
- Both inhibitor types showed effective inhibition of MMP-2 in lab tests, while animal studies indicated minimal long-term organ accumulation and potential tumor targeting in later phases.
Article Abstract
Excess matrix degradation is one of the hallmarks of cancer and is an important factor in the process of tumor progression. It is implicated in invasion, metastasis, growth, angiogenesis and migration. Many characteristics of matrix metalloproteinases (MMPs) make them attractive therapeutic and diagnostic targets. MMP expression is upregulated at the tumor site, with localization of activity in the tumor or the surrounding stroma, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'-[123I] iodo-biphenyl-4-sulfonylamino)-3-methyl-butyric acid (9) and 2-(4'-[123I] iodo-biphenyl-4-sulfonylamino)-3-methyl-butyramide (11), their unlabelled standards and precursors were synthesized. Radioiodination was conducted by electrophilic aromatic substitution of the tributylstannyl precursors and resulted in radiochemical yields of 70+/-5% (n=6) and 60+/-5% (n=4), respectively. In vitro zymography and enzyme assays showed for both hydroxamic acid and carboxylic acid compounds a good inhibition activity and a high selectivity for MMP-2. In vivo biodistribution in NMRI mice showed no long-term accumulation in organs and the possibility to accumulate in the tumor in a later phase of this study.
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| http://dx.doi.org/10.1016/j.apradiso.2004.12.009 | DOI Listing |
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