Molecular Imaging using Lanthanide Chelates
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Abstract
Multiple targets and various approaches to signaling and/or therapeutic intervention are under investigation. A main target of interest is the 18 kD protein, the Peripheral Benzodiazepine Receptor (PBR). PBR is found primarily in the mitochondria and is known to be associated with responsiveness to reactive oxygen species, apoptosis and steroidogenesis. PBR expression is upregulated in some cancers, and its density has been correlated with metabolic status of the cell. These observations make PBR an attractive target for the delivery of contrast agents and therapeutics to diseased tissue. Recently we prepared a PBR targeted imaging agent based on our relatively unique lanthanide chelate chemistry. The lanthanides are brightly luminescent, show promise for early cancer detection and can even be used as multi modal agents by simple exchange of the chelated lanthanide ion. In-vitro and in-vivo investigations along with new synthetic methodologies are being developed in our laboratory. Some of these new agents have also demonstrated promise as in-vitro diagnostic stains for use in histopathology. In addition, we are developing near-infrared fluorochromes, PET agents, and MR signaling agents that are smart, can precipitate selectively or can provide both a signature and a therapeutic effect. Also under intense investigation are the unique spectroscopic properties of the lanthanide chelates.