MRI IMAGING OF TUMOR HYPOXIA

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The field of diagnostic radiology is undergoing a quiet revolution. While radiology in the past has focused on anatomy, techniques have emerged over the past decade to non-invasively interrogate tissue/tumor functions and molecular phenotypes. The goal of this new project is to incorporate and improve the application of functional and molecular imaging to the development of redox active anti-cancer drugs. Prior work by our group and others has identified a number of useful MR imaging endpoints for drug therapy, including diffusion MRI, dynamic contrast enhanced (DCE) MRI, and 1H/31P magnetic resonance spectroscopy (MRS). Because these are developed and only need application, these endpoints are contained in the biomarkers core C. The aims of this project are to develop newer redox-sensitive contrast mechanism for use in this program. Specifically, we will investigate (Aim 1) R2* imaging (also known as blood oxygen level dependent, or BOLD, imaging), (Aim 2) DCE imaging with high molecular weight contrast agents, and (Aim 3) novel contrast agents that will reversibly interact with serum thiols. All aims will focus on developing imaging approaches to empirically identify, prior to therapy, those patients most likely to benefit from redox active anti-cancer drugs ("theragnostics"). Such a capability could have an important impact on clinical trial design and patient management. An important secondary goal will be the use of imaging biomarkers to monitor response after commencement of therapy. These approaches will primarily be conducted in pre-clinical anaimal models, and translated to the clinical trials as soon as appropriate.