Application of a biodegradable, macrocyclic, polydisulfide-based contrast agent for monitoring tumor angiogenesis using dynamic contrast enhanced MRI

A novel biodegradable polydisulfide-based macrocyclic contrast agent was developed for dynamic contrast enhanced (DCE) MRI. The new macromolecular agent selectively extravasates from leaky tumor vessels, while minimizing potentially toxic side effects due to cleavage of disulfide bonds incorporated into its backbone. This agent was utilized to study anti-angiogenic effects of Bumetanide, an inhibitor of NKCC cotransporters that has recently exhibited anti-tumoral capabilities, in colon cancer xenografts. DCE-MRI revealed that the polydisulfide contrast agent is able to detect significant reductions in the permeability and plasma volume fraction parameters, which were then verified by a decrease in CD31 expression upon IHC analysis.

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