Cest Liposomes Provide Multi-Color MRI Contrast for Cell Imaging
Michael T. McMahon1, Yah-el Har-el2, Assaf A. Gilad2, George Sgouros2, Jeff W.M. Bulte2 and Peter C.M. van Zijl1, (1)F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, (2)Russell H. Morgan Dept. of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21205

Current cellular MR imaging relies on metallic contrast agents to produce hypo- or hyper-intense spots where cells are located. We present a series of protein-containing liposomes for cellular MRI. These proteins can be selectively activated by frequency-specific RF irradiation where the contrast produced relies on chemical exchange saturation transfer (CEST) from protein amide protons to water. The proteins can be distinguished by the saturation frequency dependence of their particular protein content, also referred to as ‘colors'. By incorporating CEST agents into liposomes, we can limit their interactions with biological media and avoid local dilution of agent. CEST liposomes are capable of producing significant contrast at nM concentrations of liposome. A variety of poly-peptides capable of producing a CEST effect were encapsulated within liposomes, including Poly-L-Ornithine (PLO), Poly-L-Arginine (PLA), and Poly-L-Lysine (PLL). The liposomes display similar frequency dependence of MR contrast to free PLO, PLA, and PLL. Next, it was determined whether the liposomes would enter cells and maintain cell viability. 9L rat glioma cells were incubated overnight in 96 well plates with a series of liposome concentrations, and an MTT assay was used to assess the cell viability. For this level of confluent cells, concentrations of 0.32 nM PLL liposome (18mg/mL PLL solution encapsulated in liposomes) in the media were tolerated, producing viable cells. This new agent, which is composed of purely natural substances should prove useful for future cell tracking studies, and potentially as a diagnostic agent as well.

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Sensors and Bio-Imaging Contrast Agents at the Cellular Level

The Preliminary Program for 2007 Annual Meeting