AN MRI CONTRAST AGENT THAT DETECTS GENE EXPRESSION

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Our laboratory has developed a magnetic resonance contrast agent that is an in vivo indicator for gene expression. This agent is activated by enzymatic cleavage with the common reporter gene, beta-galactosidase. The patterns of gene expression observed in vivo can yield clues to underlying gene regulation processes; this has important ramifications for understanding disease pathogenesis and therapy. Preliminary results show that the agent is very effective in a Xenopus embryo system, wherein the agent is introduced by microinjection. However, little is known about the uptake of the agent by cells, or the distribution of the agent in tissues in the absence of microinjection. In order to advance our understanding of this agent, we propose to study its behavior in cell culture systems, in a mouse tumor model, and in transgenic mice. We will examine the movement and activation of the agent in these systems, investigate the efficacy of liposomal delivery systems, and explore how modifications to the agent affect its activation efficiency and transport properties.