In vitro Relaxometric and Luminescence Characterization of P792 (Gadomelitol, Vistarem®), an Efficient and Rapid Clearance Blood Pool MRI Contrast Agent

Abstract

AbstractP792 (Gadomelitol, Vistarem®), a hydrophilic high molecular weight (MW = 6473 g/mol) derivative of DOTA‐Gd is a rapid clearance blood pool agent (RCBPA) characterized by high proton relaxivities r1 and r2 at 310 K in the current range of clinical imaging magnetic fields. Luminescence data of the EuIII complex, as expected for this type of DOTA derivative, agree with the presence of one water molecule in the first coordination sphere of the lanthanide ion. The stability of the water proton longitudinal relaxation rate in the presence of zinc(II) and phosphate ions showed that the transmetallation by ZnII ions is negligible. The temperature dependence of the water oxygen‐17 transverse relaxation rate gave a τM smaller than 100 ns at 310 K. No significant increase of longitudinal or transverse relaxation rates in serum or HSA solution was noticed, precluding association with high molecular weight blood components. The proton Nuclear Magnetic Relaxation Dispersion (NMRD) profile of the water solution showed a maximum of longitudinal relaxivity between 20 and 40 MHz (r1 ≈ 40 s–1 mM–1 at 310 K). Fitting of the proton NMRD curve by the classical outersphere and innersphere models, including or not additional second sphere water molecules, gave a rotational correlation time of approximately 2 to 3 ns and a large value of the electronic relaxation time at low field (τSO ≈ 500 ps). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)