Design Principles of Responsive Relaxometric ¹⁹F Contrast Agents: Evaluation from the Point of View of Relaxation Theory and Experimental Data

Abstract

19 F magnetic resonance imaging (MRI) is a promising tool in medical diagnostics. An important class of 19 F MRI contrast agents is based on paramagnetic resonance enhancement. This effect allows an improvement in sensitivity by increasing the number of scans per unit of time or facilitates the development of responsive contrast agents that are based on changes in relaxation rates as a detection principle. In this work, Bloch− Redfield−Wangsness relaxation theory was used to predict the relaxation properties of existing lanthanoid and transition metal complexes of fluoroorganic ligands and to evaluate several design strategies for responsive contrast agents. Electron−nucleus dipole−dipole, Curie relaxation, and contact interactions were included in the model. Potential significance of chemical shift anisotropy−anisotropic dipolar shielding cross-correlation was discussed. The calculated and experimental results were well aligned. The presented model, along with the optimized field-dependent values of electronic relaxation times, could be used for the preliminary selection of the optimal metal ion for applications in 19 F MRI. The results indicate potential advantages of other metal ions in addition to Gd 3+ particularly Cu 2+ , Mn 2+ , Ni 2+ , Fe 3+ , and other lanthanoids as a part of 19 F contrast agents.

Transition metal complexes of cyclam with two 2,2,2-trifluoroethylphosphinate pendant arms as probes for 19F magnetic resonance imaging

“…The observed distances are relevant for their significant influence on the relaxation times. 30 As the trifluoroethyl group undergoes free rotation, mean distances (Table 3) are used in the following discussion, although effective distances in the solution can differ due to molecular flexibility and can be shorter. 30 Solutions of the prepared complexes underwent detailed 19 F NMR study.…”

“…30 As the trifluoroethyl group undergoes free rotation, mean distances (Table 3) are used in the following discussion, although effective distances in the solution can differ due to molecular flexibility and can be shorter. 30 Solutions of the prepared complexes underwent detailed 19 F NMR study. The T 1 and T * 2 relaxation times were measured at available magnetic fields (7.05/9.40/14.1 T, 282/376/565 MHz) at 25 and 37 °C and the results are outlined in Table 4.…”

“…A source of the T 1 shortening lies in the dipolar mechanism as the number of bonds between the metal ion and fluorine atom is too high (5) to consider a significant contact contribution and Curie relaxation can be neglected for small molecules with small magnetic moments. 30,34 The cis-O,O′-[Co(L)] species showed longitudinal relaxation times in the range 30-40 ms which is very convenient for practical utilization. It is ca.…”

Hydrazone Molecular Switches with Paramagnetic Center as 19F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging

“…The selection of the most suitable paramagnetic ion for complexation was conducted by theoretical calculations based on the Bloch–Redfield–Wangsness (BRW) theory, taking into account the electron–nucleus dipole–dipole and Curie interactions only. This was justified by an earlier review of available 19 F relaxation data for DOTA-derived paramagnetic complexes . The highest relaxation time differences from pH-induced isomerization resulted from complexes of Gd­(III), Ho­(III), Dy­(III), Er­(III), Cu­(II), or Cr­(III) (Figure S18 and Table S1).…”

“…This was justified by an earlier review of available 19 F relaxation data for DOTA-derived paramagnetic complexes. 52 The highest relaxation time differences from pHinduced isomerization resulted from complexes of Gd(III), Ho(III), Dy(III), Er(III), Cu(II), or Cr(III) (Figure S18 and Table S1).…”