Mn-bicine: A Low Affinity Chelate for Manganese Ion Enhanced MRI

The toxicity of free Mn(2+) is a bottleneck for the in vivo application of manganese ion enhanced MRI. To reduce free Mn(2+) concentration ([Mn(2+)]), a low affinity chelate reagent: N,N-bis(2-hydroxyethyl)glycine (bicine) was used. Considering the conditional association constant of Mn-bicine at pH 7.4 (10(2.9) M(-1)), (i) a 100 mM Mn-bicine solution should contain about 10 mM of free manganese ion, but (ii) free manganese will make up 3/4 of the final plasma concentration (0.5 mM) with an intravenous infusion of 100 mM Mn-bicine. The T(1) relaxivity of Mn-bicine in a 5 mM Mn-bicine solution was estimated as 5 mM(-1) sec(-1) at 24 degrees C, 7 T in a pH range of 6.8-7.5. Mn-bicine demonstrated a tendency for better contractility when employed with an isolated perfused frog heart, compared with MnCl(2). A venous infusion of 100 mM Mn-bicine (8.3 mu mol kg(-1) min(-1)) showed a minimal decrease and maintained a constant heart rate level and arterial pressure in rats, while rats infused with 100 mM of MnCl(2) showed a significant suppression of the hemodynamic functions. Thus, Mn-bicine appears to be a better choice for maintaining the vital conditions of experimental animals, and may improve the reproducibility of manganese ion enhanced MRI. Magn Reson Med 65:1005-1012, 2011. (C) 2010 Wiley-Liss, Inc.