Enzyme-activated MR Contrast Agents - Limitations

Limitations

Once the contrast agent has been activated by cleavage of the sugar group, the signal enhancing effects will only diminish if the gadolinium is washed out of the compartment containing it, or if water’s access to the metal group is again inhibited. So, to prevent permanent enhancement of the MR signal, cells must either have a way to export the gadolinium group to the bloodstream, or they must be able to replace the cleaved sugar group. There is no data in the literature indicating that either approach is feasible in vivo, suggesting that these methods may result in permanent signal amplification.

Another challenge is the delivery of the contrast agents to target cells. In the sole paper describing in vivo use of enzyme-activated MR contrast agents, the agent was delivered to embryonic cells via a micropipette. However, the authors of the paper acknowledge that this is not a feasible approach for many research projects, and it presents a clear impediment to clinical use. There is active research in using the cell’s native import machinery to load contrast agents.

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