Novel solubility-switchable MRI agent allows the noninvasive detection of matrix metalloproteinase-2 activity in vivo in a mouse model
✍ Scribed by Réjean Lebel; Beata Jastrzębska; Hélène Therriault; Marie-Michèle Cournoyer; J. Oliver McIntyre; Emanuel Escher; Witold Neugebauer; Benoit Paquette; Martin Lepage
- Book ID
- 102956404
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 918 KB
- Volume
- 60
- Category
- Article
- ISSN
- 0740-3194
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✦ Synopsis
Abstract
A novel MRI proteinase‐modulated contrast agent (PCA) was developed to detect the activity of the proinvasive enzyme matrix metalloproteinase‐2 (MMP‐2) in vivo. The PCA2‐switch agent incorporates a solubility switch, where cleavage of a peptide substrate by MMP‐2 decreases the water solubility of the agent. Evidence suggests that this leads to an accumulation of cleaved PCA2‐switch in an MMP‐2‐positive, wild‐type, MC7‐L1 mammary carcinoma tumor in a Balb/c mouse model compared to a MC7‐L1 MMP‐2‐knockdown tumor. When a scrambled peptide sequence is inserted into the agent (PCA2‐scrambled), the in vitro cleavage efficiency of MMP‐2 is markedly reduced. In vivo, PCA2‐scrambled does not accumulate in the wild‐type tumor and the pharmacokinetics is similar in both tumors. In conclusion, in vivo cleavage of PCA2‐switch by MMP‐2 results in a significant accumulation of the cleaved PCA2‐switch in an MMP‐2‐positive tumor. Magn Reson Med 60:1056–1065, 2008. © 2008 Wiley‐Liss, Inc.