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Novel solubility-switchable MRI agent allows the noninvasive detection of matrix metalloproteinase-2 activity in vivo in a mouse model.

Lebel R, Jastrzebska B, Therriault H, Cournoyer MM, McIntyre JO, Escher E, Neugebauer W, Paquette B, Lepage M
Magn Reson Med. 2008 60 (5): 1056-65

PMID: 18956456 · DOI:10.1002/mrm.21741

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.

MeSH Terms (10)

Animals Cell Line, Tumor Contrast Media Enzyme Activation Magnetic Resonance Imaging Mammary Neoplasms, Experimental Matrix Metalloproteinase 2 Mice Mice, Inbred BALB C Peptide Hydrolases

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