The major hypothesis guiding this research is that modular low-molecular weight ligands, specific for the surface of bladder cancer cells, will be clinically useful reagents. Using peptide phage display screening of live bladder cancer cells, we have discovered two families of peptides, each ten amino acids in iength which bind with high afffinity and specificity to bladder cancer cells, and which exhibit no binding to normai bladder urothelial cells. These ligands offer several potential advantages including rapid biodistribution excellent tissue/tumor penetration, and ease of conjugation to imaging reagents. The long-range goal of this research is to improve bladder cancer staging and treatment by developing novel in vivo molecular imaging reagents and novel therapeutics.
The specific aims of this study are designed to expedite future clinical studies of molecular imaging in , advanced bladder cancer.
One specific aim i s to create, and to optimize, novel magnetic resonance imaging contrast agents by conjugating the bladder cancer-specific peptides to ferromagnetic monocrystalline iron oxide nanocompounds (MlONs). The second specific aim is to create, and to optimize, novel radioscintigraphic imaging reagents by conjugaffng the bladder cancer-specific peptides to radiometal chelators. For each imaging modality, a systematic development scheme including in vitro optimization, in vivo biodistribution and pharrnacokinetics, and in vivo three-dimensional imaging is described. We believe that bladder cancer-specific, low-molecular weight ligands will someday be clinically useful reagents for improved detection and guided therapy of transitional cell carcinoma of the bladder.
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