Multiplexed magnetic resonance imaging with functionalized xenon-129 biosensors

ANYL 251

Ivan J. Dmochowski, ivandmo@sas.upenn.edu, Department of Chemistry, University of Pennsylvania, 231 South 34th St., Philadelphia, PA 19104-6323
Functionalized xenon biosensors offer an attractive alternative to conventional MRI contrast agents due to the chemical shift sensitivity and large magnetic signal of hyperpolarized Xe-129. Our group is working to develop this technology for in vivo biosensing. Currently, cryptophane-A is the organic cage molecule with the highest known xenon affinity (KA ~3900M-1 in C2D2Cl4 at 298 K). New organic cages with higher xenon binding affinities have been designed. Synthetic details, Xe binding, and cell uptake studies will be presented. Finally, we have developed Xe biosensors for detecting matrix metalloproteinases (MMPs), which are secreted by cancer cells. Cryptophane-A was functionalized with a MMP-7 peptide cleavage substrate. This biosensor molecule exhibited comparable cleavage kinetics to known MMP-7 substrates as well as a Xe-129 NMR chemical shift change upon substrate cleavage. Catalytic biosensing by Xe-129 magnetic resonance offers a promising strategy for the early detection of cancer.