The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn
2+ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn
2+ ions in the extracellular space.
In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn
2+ ions, as the addition of Ca‐DO2A to a solution of MnCl
2 causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn
2+ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the
in vivo, instantaneous, drop in SE% (percent signal enhancement) in
T1‐weighted images is taken as evidence of the sequestration of extracellular Mn
2+ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice,
T1 decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd.
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