: Over the last thirty years many noteworthy advances in the early detection of breast, colon, and prostate cancer have improved treatment and, in some instances, improved outcomes. Yet during this timeframe, the incidence of cancer continued to increase, morbidity from treatments (i.e., surgery, radiation and chemotherapy) remained unacceptable, and survival only improved marginally. The subject of this proposal is the application of a novel paramagnetic site-targeted contrast """"""""platform technology"""""""" for sensitive and specific imaging of molecular epitopes expressed on tumor neovasculature alone and in combination with the local delivery of chemotherapeutic agents to these sites. av?3-integrin nanoparticles effectively target solid animal tumors and human xenografts to provide marked MR T1-weighted contrast and potent anti-tumor therapy. Unfortunately, no single vascular biosignature is ubiquitous across all solid tumors. Therefore, tumors must be noninvasively interrogated against a broader panel of targeted agents in order to individualize therapy with the appropriate single or combination of ligand directed nanoparticles. This program, we will expand utility of this successful nanotechnology platform to additional early biosignatures that may be targeted alone or simultaneously for the most effective diagnostic and chemotherapeutic response. In parallel, we will develop noninvasive imaging software and hardware to exploit the unique opportunity presented by perfluorocarbon nanoparticles for 19F MR spectroscopy, 19F imaging, and 1H/19F hybrid imaging. The use of 19F spectroscopy and imaging will not only add quantitative and spectral dimensionality to targeted nanoparticle applications, but 19F imaging can also eliminate the need for baseline digital subtraction of images, which is time-consuming and prone to error. Interleaved 1H/19F hybrid imaging will minimize motion artifacts, eliminate image registration issues, confirm contrast identification and shorten patient scanning times.
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