A systematic investigation of the NMR relaxation properties of Fe(iii)-EDTA derivatives and their potential as MRI contrast agents

Abstract

We report a detailed investigation of the potential as magnetic resonance imaging (MRI) contrast agents of Fe(III) complexes with H4EDTA derivatives containing different spacers: trans-cyclohexane-1,2-diamine (t H4CDTA), cis-cyclohexane-1,2-diamine (c H4CDTA),...

Liposomal MRI probes containing encapsulated or amphiphilic Fe(iii) coordination complexes

“…46 The magnetic field dependence of the three complexes from 1.4 to 9.4 T does not change markedly, although a slight dip is observed at 4.7 T for [Fe(NOHP)] 2+ and [Fe(NOTP)] 3− . Although studies of the full field strength relaxivity dependence are needed, it is interesting to note that NMRD profiles recently reported for EDTA derivatives of Fe( iii ) complexes, 14,22 show a dispersion in r 1 from 10 MHz to 100 MHz with an increase at higher fields, a profile that is not very different than that observed here.…”

“…46 The magnetic field dependence of the three complexes from 1.4 to 9.4 T does not change markedly, although a slight dip is observed at 4.7 T for [Fe(NOHP)] 2+ and [Fe(NOTP)] 3− . Although studies of the full field strength relaxivity dependence are needed, it is interesting to note that NMRD profiles recently reported for EDTA derivatives of Fe(III) complexes, 14,22 show a dispersion in r 1 from 10 MHz to 100 MHz with an increase at higher fields, a profile that is not very different than that observed here. The T 1 and T 2 water proton relaxation times were measured for LipoA, LipoB and LipoC as a function of concentration of the iron complex in the liposome to obtain the relaxivities of the paramagnetic liposomes on a per iron and per particle basis as described (Table 1 and Table S3 †) As anticipated, the relaxivity values for the liposomal formulations vary substantially based on whether the iron complex is encapsulated or incorporated into the liposome.…”

“…Fe( iii ) complexes were investigated in early studies of MRI contrast agents, 21 but interest decreased as Gd( iii ) agents were developed. Interest in Fe( iii )-based MRI probes has increased recently with several new reports highlighting the challenges of their development as coordination complexes 11,12,14,15,22,23 and in nanostructures. 24…”

“…Fe(III) complexes were investigated in early studies of MRI contrast agents, 21 but interest decreased as Gd(III) agents were developed. Interest in Fe(III)-based MRI probes has increased recently with several new reports highlighting the challenges of their development as coordination complexes 11,12,14,15,22,23 and in nanostructures. 24 Our laboratory focuses on the development of transition metal MRI probes, including CEST agents (Fe(II), Co(II) and Ni(II)), 13,25 liposomal CEST agents 26 and relaxivity agents such as high-spin Fe(III) complexes.…”

Fe(III) T1 MRI Probes Containing Phenolate or Hydroxypyridine-Appended Triamine Chelates and a Coordination Site for Bound Water

“…2,14 Similar to gadolinium-based contrast agents, high-spin Fe(III) complexes shorten the T 1 relaxation times of water protons through inner-sphere, second-sphere, and outer-sphere water interactions. 10,15,16 Dipole−dipole relaxation mechanisms are dominant, and these interactions are governed by several correlation times including the rotational correlation time (τ r ) of the paramagnetic complex in solution, the exchange rate of the coordinated water molecule (k ex = 1/ τ m ), the distance of the paramagnetic metal ion and the protons of the coordinated water (r MH ), and the electronic relaxation times of the paramagnetic metal ion (τ s ). 17 However, Fe(III) complexes, in contrast to Gd(III)-or Mn(II)-based contrast agents, may have electronic relaxation rates that are sufficiently rapid to limit relaxivity at clinical magnetic field strengths (1.5−3 T).…”