Synthesis and visualization of a membrane-permeable MRI contrast agent

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Abstract
The study of in vivo developmental events has undergone significant advances with the advent of biological molecular imaging techniques such as computer enhanced light microscopy imaging, positron emission tomography (PET), micro-CT, and magnetic resonance imaging (MRI). MRI has proven to be a particularly powerful tool in clinical and biological settings. Images can be acquired of opaque living animals, with the benefit of tracking events of extended periods of time on the same specimen. Contrast agents are routinely used to enhance regions, tissues, and cells that are magnetically similar but histologically distinct. A principal barrier to the development of MR contrast agents for investigating developmental biological questions is the ability to deliver the agent across cellular membranes. As part of our research, we are investigating a number of small molecules that facilitate transport of charged and uncharged species across cell membranes. Here we describe the synthesis and testing of a Gd(III)-based MR contrast agent conjugated to polyarginine that is able to permeate cell membranes. We confirmed cellular uptake of the agent using two-photon laser microscopy to visualize a Eu(III) derivative of the contrast agent in cell culture, and verified this uptake by T 1 analysis of the Gd(III) agent in cells.