Synthesis of lanthanide chelates for biomedical imaging

Lanthanide chelates are a somewhat unique class of molecules that have proven to be useful in the biomedical field as contrast agents for disease detection. This is due to many factors including their extremely large Stokes' shift, generally around 300 nm, and millisecond fluorescent lifetimes. The ability of these molecules to produce fluorescence in the low or zero-background regime as well as low cytotoxicity makes this class of molecules excellent candidates for use as contrast agents for a wide variety of applications in biological settings. Here we present the simple preparation and spectroscopic characterization of a new Europium chelate contrast agent, based on the 1, 4, 7, 10-tctraazacyclododecane macrocycle (cyclen). Eu-QF(CTME) produces a bright pinkish red luminescence when excited with low photon fluxes of UV light, indicating its potential for use in the field of biomedical imaging as a fluorescent probe. To determine the efficacy of this molecule as a fluorescent probe for disease detection, both animal testing as well as testing in a human tissue culture system was preformed. The well documented DMBA-treated Golden Hamster Cheek pouch epithelial cancer model was employed with Eu-QF(CTME) used as a topical agent for the detection of diseased tissue. In this preliminary study, the agent was observed to associate with malignant lesions, as well as dysplastic tissue. This suggests that Eu-QF(CTME) could be used as a contrast agent to aid in identifying oral precancer and cancer lesions. The results from the cell uptake experiments demonstrates the potential of this molecule as a stain for cancer cells.