Molecular imaging is a powerful tool that has the ability to elucidate biochemical mechanisms and signal the early onset of disease. Overexpression of the peripheral benzodiazepine receptor (PBR) has been observed in a variety disease states, including glioblastoma, breast cancer, and Alzheimer's disease. Thus, the PBR could be an attractive target for molecular imaging. In this paper, the authors report cellular uptake and multimodal (MRI and fluorescence) imaging of PBR-overexpressing C6 glioblastoma (brain cancer) cells using a cocktail administration approach and a new PBR targeted lanthanide chelate molecular imaging agent.

[reaction: see text] Receptor-mediated imaging and therapy of diseased tissue is rapidly gaining favor in the medical community. The synthesis and facile aqueous/organic coupling of a peripheral-type benzodiazepine receptor ligand to a cyclen-based fluorophore is described herein. The contrast agent QM-CTMC-PK11195, when chelated with lanthanides, produces bright luminescence and good MRI contrast and can potentially serve as an imaging and demarcation agent for certain types of cancers.

Lanthanide chelates are a somewhat unique class of molecules that have proven to be useful in the biomedical field due to their extremely large Stokes' shift and long fluorescent lifetimes. The ability of these molecules to produce fluorescence in the low- or zero-back-ground regime 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 preparation, spectroscopic characterization, and application of a new terbium chelate contrast agent, based on the 1,4,7,10-tetraazacyclododecane macrocycle (cyclen), for detection of early-stage malignant lesions in the Syrian hamster cheek pouch. Tb-P(CTMB) delivers bright blue-green luminescence when excited with low photon fluxes of UV light. As a pilot study, the DMBA-treated Golden Hamster Cheek pouch epithelial cancer model was employed and Tb-P(CTMB) was used as a topical agent for the visual detection of diseased tissue. In this preliminary study the agent tended to associate with early-stage malignant lesions, suggesting that Tb-P(CTMB) could be used as a contrast agent to aid in identifying early-stage oral cancer lesions.