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

Abstract

Keywords: P792 / MRI contrast agent / NMRD / Luminescence / Oxygen-17 relaxometry P792 (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 r 1 and r 2 at 310 K in the current range of clinical imaging magnetic fields. Luminescence data of the Eu III 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 Zn II ions is negligible. The temperature dependence of the water oxygen-17 transverse relaxation rate gave a τ M smaller than 100 ns at 310 K. No significant increase of longi-

Joint analysis of ESR lineshapes and 1H NMRD profiles of DOTA-Gd derivatives by means of the slow motion theory

“…The complexes are hydrophilic derivatives of DOTA-Gd, with molecular masses of 5.6 and 6.5 kDa, respectively. The NMRD data have been taken from Vander Elst et al 60,61 for P760 and P792, respectively. In both cases the relaxation data were collected at 310 K. The concentration of P760 was 0.19 mMol, while for P792 two concentrations were used, 0.285 and 1 mMol.…”

“…60) and τ M = 80 − 100 ns (Ref. 61) for P760 and P792, respectively, depending on the applied fitting strategy. In addition, the reorientational correlation times were estimated as being about τ R = 2.2 ns (from 2 H relaxation data) and τ R = 1.8 ns (from Stokes-Einstein equation using the molecular volume from photon correlation spectroscopy) for P760, 60 61 Analyzing the NMRD data for both complexes in terms of inner-and outer-sphere contributions, the authors obtained τ R = 1.8 ns (for τ M = 320 ns) for P760 (Ref.…”

“…60) and τ R = 1.7 ns (for τ M = 96 ns) for P792. 61 The description of the nuclear relaxation used in both papers 60,61 was based on the classical Solomon-Bloembergen-Morgan 2-4 formula for the innersphere and on the outer-sphere model proposed by Hwang and Freed. 39 We choose to start the analysis from the NMRD profile for P760.…”

“…9(b)] but the calculated ESR line stays too narrow. The static ZFS parameters in line I, It is very important in this context to investigate the influence of the concentration of the P792 complex on the ESR lineshape (while the NMRD profiles remain almost unaffected 61 ). We show ESR spectra for P792 collected for the concentration of 1 mMol, and compared with the spectra for 0.285 mMol (the subject of the analysis above), in Fig.…”

New synthesis of a high molecular weight ligand derived from dota; thermodynamic stability of the MRI contrast agent formed with gadolinium

“…The complexes of P1041 with gadolinium were described in previous works (5)(6)(7)(8) relating, in particular, to relaxivity, transmetallation and modelling, but no reports concerned the thermodynamic study of the P1041-Gd 3þ system. There is increasing evidence that chemical stability of the chelate has a great influence on the exchange between Gd 3þ and other body metal ions (notably Zn 2þ , Cu 2þ or Ca 2þ ) which can, in turn, have biological consequences such as accumulation of Gd 3þ in various organs such as bones or skin, interaction with scintigraphic procedures, increased zincuria or interaction with metaldependent biological systems such as enzymes (9).…”