Development of Spin Probes for Cell-tagging and Oximetry

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DESCRIPTION (provided by applicant): Non-invasive methods capable of detection and imaging of molecular targets, cells and tissue abnormalities will be valuable in biomedical research. Cell labeling with magnetic nanoparticulate contrast agents has emerged as a powerful tool for in vivo imaging using MRI technique. The objective of this proposal is to develop novel multifunctional paramagnetic probes for use in magnetic resonance-based imaging of cells and tissues. We have identified a new class of paramagnetic crystalline materials that can be directly detected by electron paramagnetic resonance (EPR) spectroscopy and imaging with markedly higher sensitivity and spatial resolution. They are composed of stacks of neutral free radicals of lithiated phthalonaphthalo- and anthracyanine macrocycles. The EPR spectrum of these probes is characterized by a single and very narrow EPR absorption due to strong exchange coupling between the unpaired electrons. In addition, the particulates will have the unique advantages of sensing and reporting cellular and tissue oxygen levels with remarkable oxygen sensitivity and biostability enabling precise, accurate and repeated measurement and mapping of oxygen concentration in tissues over extended periods of time. The particulates can be prepared in submicron sizes and efficiently internalized by endocytosis without encapsulation, coatings or attachment to specific receptors. The unique properties of these particulates can be exploited by internalizing them into cells and in specific tissues to visualize cell proliferation, migration and trafficking, similar to superparamagnetic particulates used in MRI. The following five specific aims are proposed: 1. Design, synthesis, characterization and formulation of novel paramagnetic spin particulates for use as biosensors of oxygen, cell-tracking and imaging; 2. Characterization of in vitro and in vivo distribution and toxicity of the particulates to cells and tissues; 3. Internalization (cellular uptake) and characterization of particulates in cells; 4. Establishment of the particulate spin probes for cellular and in vivo tissue and vascular oximetry applications; 5. Establishment of the particulate spin probes for in vivo applications such as whole-body imaging of particulate uptake and distribution, particulate uptake by cells and cell tracking. The availability of these probes will enhance our ability to perform biomedical imaging and offer exciting new opportunities in the field of cell therapy and tissue engineering.