Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1361278 | Bioorganic & Medicinal Chemistry Letters | 2012 | 5 Pages |
Hypoxia occurs in various diseases, including cancer, ischemia, and acute and chronic vascular diseases. Here we describe the design and synthesis of the first hypoxia-sensitive MRI contrast agents, SAGds. SAGds showed a pH-dependent r1 relaxivity change associated with intramolecular chelation of the nitrogen atom of the sulfonamide moiety to the Gd3+ center. There was a correlation between the pKa of the r1 relaxivity change and the sum of the Hammett σ constants of substituents on the aromatic ring. Among the synthesized compounds, 4NO22MeOSAGd was selectively reduced to the amine by rat liver microsomes under hypoxic conditions, resulting in a 1.8-fold increment of the r1 relaxivity owing to the change in pKa of the arylsulfonamide moiety. This enhancement of the r1 relaxivity could be clearly detected in T1-weighted MR images. Thus, 4NO22MeOSAGd is a ‘smart’ MRI contrast agent for the detection of hypoxia under physiological conditions.
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