This proposal describes the development of hyperpolarized-129Xenon (HP-Xe)-based probes for magnetic resonance imaging (MRI) of two biomarkers of inflammation and brain injury, the peripheral benzodiazepine receptor (PBR) and the neurotrophic protein, S100B. Molecular imaging (MI) is an emerging discipline that tries to non-invasively visualize specific biomolecules in living organisms and has many medical applications with immense commercial potential. For example, MI-based biomarkers will allow for better treatment of disease through earlier and more precise diagnosis. In addition, they will help to shorten pre-clinical and clinical drug-development protocols by more sensitively and quantitatively measuring the biological actions of new medications. The sensitivity of positron emission tomography (PET) and single photon emission computed tomography (SPECT) have led to the widespread use of these technologies for imaging specific bio-molecules in vivo. However, PET and SPECT have very poor spatial resolution (mm-cm) and use probes containing short-lived radioactive isotopes which emit tissue damaging ionizing radiation. MRI, on the other hand, utilizes relatively harmless radio-waves to image living organisms at close to cellular resolution (25-100 We are proposing to synthesize probe molecules that can be used in conjunction with magnetic resonance imaging (MRI) to non-invasively take very high resolution pictures of the distribution of proteins called peripheral benzodiazepine receptors (PBR) and S100B in the tissues and brains of human patients. It has been previously demonstrated that examining the distribution of PBR and S100B in this manner will help us to better diagnose, monitor progression of and treat serious diseases such as multiple sclerosis, atherosclerosis, Alzheimer's disease and Parkinson's disease.Public Health Relevance
