Inorganic Chemistry, Vol.40, No.9, 2170-2176, 2001
Thermodynamic stability and kinetic inertness of MS-325, a new blood pool agent for magnetic resonance imaging
Stability constants were measured for complexes formed between a modified DTPA ligand and the metal ions Gd(III), Eu(III), Fe(III), Ca(II) Cu(II), and Zn(II) at 25 degreesC in 0.1 M NaClO4. The gadolinium complex of this ligand is MS-325. a novel blood pool contrast agent for magnetic resonance imaging currently undergoing clinical trials. Stability constants were determined by 4 different methods: direct pH titration, pH titration with competition by EDTA, competition with DTPA using an HPLC-MS detection system, and competition with Eu(III) by monitoring equilibrium by luminsecence spectroscopy. The 1:1 stability constants, log beta (101) are the following: Gd, 22.06 (23.2 in 0.1 M Me4NCl): Eu, 22.21; Fe, 26.66; Ca, 10.45; Cu, 21.3; Zn, 17.82. The exchange kinetics of the Gd complex, MS-325, with the radioactive tracer (EU)-E-152,154 were studied at 25 degreesC: in 0.1 M NaClO4. The exchange reaction has acid-dependent and acid-independent terms. The rate expression is given by the following: R = k(a)[GdL][H](2) + k(b)[GdL][Gd][H] + k(c)[GdL][Gd]. The rate constants were determined to be the following: ka = 1.84 x 10(6) M(-2)min(-1), k(b) = 2.87 x 10(3) M(-2)min(-1), k(c) = 3.72 x 10(-3) M(-1)min(-1). MS-325 is 2-3 times more stable than GdDTPA at pH 7.4 and is 10-100 times more kinetically inert.