The field of diagnostic radiology is undergoing a quiet revolution. While radiology in the past has focused onanatomy, techniques have emerged over the past decade to non-invasively interrogate tissue/tumorfunctions and molecular phenotypes. The goal of this new project is to incorporate and improve theapplication of functional and molecular imaging to the development of redox active anti-cancer drugs. Priorwork 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 resonancespectroscopy (MRS). Because these are developed and only need application, these endpoints arecontained in the biomarkers core C.
The aims of this project are to develop newer redox-sensitive contrastmechanism for use in this program. Specifically, we will investigate (Aim 1) R2* imaging (also known asblood oxygen level dependent, or BOLD, imaging), (Aim 2) DCE imaging with high molecular weight contrastagents, and (Aim 3) novel contrast agents that will reversibly interact with serum thiols.
All aims will focus ondeveloping imaging approaches to empirically identify, prior to therapy, those patients most likely to benefitfrom redox active anti-cancer drugs ('theragnostics'). Such a capability could have an important impact onclinical trial design and patient management. An important secondary goal will be the use of imagingbiomarkers to monitor response after commencement of therapy. These approaches will primarily beconducted in pre-clinical anaimal models, and translated to the clinical trials as soon as appropriate.
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