Ultra-Sensitive MR Probes for Molecular Diagnosis of Lung Cancer

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DESCRIPTION (provided by applicant): The long-term goal of this research is to develop ultra-sensitive magnetic resonance imaging (MRI) probes that can provide cancer-specific detection of lung tumors by MRI. MRI is a clinical imaging technique that has broad applications in non-invasive diagnosis and post-therapy assessment for cancer. Although Gd-DTPA (Magnevist.) and other small molecular weight agents work well for dynamic contrast enhancement MRI applications, these agents are not very sensitive (lower limit of detection is ~10-4 M) and therefore cannot be used for detecting specific biological markers in vivo. In this application, we will investigate the use of superparamagnetic polymeric micelles (SPPM) that are loaded with a cluster of magnetite nanoparticles for molecular imaging of lung cancer. This platform demonstrated ~20 pM sensitivity of detection by MRI that will be essential for diagnosing lung cancers. A novel class of lung cancer-targeting peptides (LCPs) identified from phage screening will be functionalized on the surface of SPPM to target lung cancer cells. The isolated peptides demonstrated remarkable binding affinities (<nM) and cell specificities (20-1000 fold) to discriminate between different cell types. Our central hypothesis is that LCP-encoded SPPM will allow for highly sensitive and specific diagnosis of different types of lung cancer in an orthotopic lung tumor model in athymic nude mice. To test this hypothesis, we will carry out the following specific aims: (1) Establish ORS method and optimize SPPM compositions to enhance ORS contrast; (2) produce and characterize LCP-encoded SPPM in vitro; and (3) validate LCP-encoded SPPM for diagnosis of lung cancer in vivo. Successful execution of this application will establish the technology foundation and preclinical efficacy of the micelle platform for non-invasive diagnosis of lung cancer. PUBLIC HEALTH RELEVANCE: A combination of novel MRI imaging method and ultra-sensitive molecular probes will be developed to provide cell-specific characterization of lung tumors. This knowledge can facilitate timely intervention of lung cancer to achieve personalized medicine.