The purpose of the work was to set-up a simple method to evaluate the contribution of Mn2+ ions in the intra- and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by silencing the relaxation enhancement arising from Mn2+ 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 Mn2+ ions, as the addition of Ca-DO2A to a solution of MnCl2 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 Mn2+ 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 T-1-weighted images is taken as evidence of the sequestration of extracellular Mn2+ ions upon addition of Ca-DO2A. By applying the method to B16F10 tumor bearing mice, T-1 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.
MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment / E. Gianolio, F. Arena, E. Di Gregorio, R. Pagliarin, M. Delbianco, G. Baio, S. Aime. - In: NMR IN BIOMEDICINE. - ISSN 0952-3480. - 28:9(2015 Sep), pp. 1104-1110. [10.1002/nbm.3349]
MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment
R. Pagliarin;
2015
Abstract
The purpose of the work was to set-up a simple method to evaluate the contribution of Mn2+ ions in the intra- and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by silencing the relaxation enhancement arising from Mn2+ 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 Mn2+ ions, as the addition of Ca-DO2A to a solution of MnCl2 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 Mn2+ 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 T-1-weighted images is taken as evidence of the sequestration of extracellular Mn2+ ions upon addition of Ca-DO2A. By applying the method to B16F10 tumor bearing mice, T-1 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.File | Dimensione | Formato | |
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