title: Mn-bicine: a low affinity chelate for manganese ion enhanced MRI.
abstract: 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°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 μmol 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.
authors.affiliation: Department of Regulatory Physiology, Dokkyo Medical University School of Medicine, Tochigi, Japan. yseo@dokkyomed.ac.jp
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Seo
authors.forename: Keitaro
authors.initials: K
authors.lastname: Satoh
authors.forename: Kazuto
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hironobu
authors.initials: H
authors.lastname: Morita
authors.forename: Akira
authors.initials: A
authors.lastname: Takamata
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogino
authors.forename: Masataka
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D007089:Image Enhancement / Q000379:methods*; D007477:Ions; D008279:Magnetic Resonance Imaging / Q000379:methods*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D008345:Manganese / Q000737:chemistry; D011892:Rana catesbeiana; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D007477:Ions; C027494:N,N-bis(2-hydroxyethyl)glycine; D008345:Manganese; D005998:Glycine