Matrix metalloproteinase and carbonic anhydrase detection based on ¹⁹F MRI and fluorescence
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Abstract
Zinc metalloproteins are heavily involved in a wide variety of human diseases,¹ such as rheumatoid arthritis, periodontitis, and cancer. Matrix metalloproteinase (MMP) and carbonic anhydrase (CA) are two zinc containing enzymes that are seen as attractive biomarkers for a multitude of pathological conditions, due to their overexpression in these diseases as well as their role in the spread and metastasis of cancer cells. Therefore, we focused on creating probes designed to track the location and relative concentration of matrix metalloproteinase and carbonic anhydrase through fluorescence and ¹⁹F MRI. In the first project, an inhibitor and a set of fluorophores were synthesized to bind to MMPs and display a ‘turn on’ signal. In the second project, a probe was designed to detect MMP activity through ¹⁹F MRI. Finally, in the third project, a probe was created to detect CA activity via ¹⁹F MRI. Here, we describe the synthesis and characterization of these probes and report preliminary UV and fluorescence response along with ¹⁹F NMR T₁ and T₂ relaxivity.