Composite MR contrast agents for conditional cell-labeling

Abstract

Gadolinium-chelates (Gd-DTPA) and superparamagnetic particles of iron oxide (SPIO) are two commonly used MR contrast agents that exhibit inherently different relaxation properties. These two agents have been used to label cells ex-vivo to generate signal contrast with respect to background tissue when introduced to a tissue-of-interest. Assuming minimal mutual interaction between these two agents, we were motivated to investigate the creation of composite relaxation properties by mixing the two in aqueous solutions for conditioning cell labeling. Concentration-dependent relaxivity coefficients were first obtained from each contrast agent, independently, in saline solution at 3 Tesla. These coefficients were then used to predict both the R-1 and R-2 relaxation rates of a composite contrast agent using a linear model combining the effects of both contrast media. The predicted relaxation rates were experimentally confirmed from 25 composite solutions (combinations of SPIO-concentration ranging from 0 to 1 mu g/mL and Gd-DTPA-concentration ranging from 0 to 0.20 mM). We show that the combination of SPIO and Gd-DTPA in an aqueous solution exhibits unique and predictable relaxivity properties that are unattainable via the individual use of either agent. The method may be applied to create "user-tunable" contrast conditions for the visualization of magnetically labeled cells in the context of cell replacement therapy. (c) 2008 Wiley Periodicals, Inc.