Prototropic Exchange Governs T₁ and T₂ Relaxivities of a Potential MRI Contrast Agent Nanozeolite Gd−LTL with a High pH Responsiveness

Abstract

Aqueous suspensions of lanthanide exchanged zeolite LTL have been investigated by 1 H, 17 O NMR, and EPR relaxivity studies. Both the longitudinal and the transverse relaxivity of these Gd 3+ loaded materials are strongly pH dependent and therefore, they have great potential as pH responsive contrast agents. For example, LTL-nanocrystals loaded with 3.5 wt% Gd show a dramatic decrease in the longitudinal relaxivity from 32 to 7 s -1 mM -1 (7.5 T and 25 °C) when going from pH 4 to 9. 1 H and 17 O NMR show that this phenomenon can be rationalized by a decrease in proton mobility between the zeolite interior and the exterior due to a change from a fast prototropic exchange to a three orders of magnitude slower water exchange mechanism. The same material also has a high transverse relaxivity (98 s -1 mM -1 at 7.5 T, 25 °C, and pH 5 as measured with the CPMG pulse sequence), which is governed by proton exchange too, while water diffusion plays a minor role. The high relaxivities and pH dependence render Gd-loaded LTL materials promising pH responsive contrast agents. Since the r 2 /r 1 ratio of the designed probe strongly increases with the magnetic field strength, these materials are expected to be applicable for both T 1 and T 2 weighted imaging at low and high fields, respectively.

Highly Loaded Semipermeable Nanocapsules for Magnetic Resonance Imaging

“…Here we observe a strong dependence of the relaxivity on the concentration of the encapsulated contrast agent (Figure 3a). Decreasing the amount of encapsulated contrast agent from the maximum concentration of 0.2 M to the minimum concentration of 4 × 10 −3 M Gadobutrol solution inside the nanocarriers led to an increase of the relaxivity from ≈22 to ≈40 s −1 mmol −1 L. As the relaxivity of a contrast agent is usually independent of its concentration, this trend is an intrinsic effect of the confinement in nanocapsules and was observed before for polyurea nanocapsules, [45] for nanozeolites [61] as well as for silica nanoparticles. [29,62] It can be attributed to a saturation effect.…”

Surface PEG Grafting Density Determines Magnetic Relaxation Properties of Gd-Loaded Porous Nanoparticles for MR Imaging Applications

“…Our previous investigations on the relaxation mechanism revealed that above pH 7 the water structuring inside the zeolite is disrupted by ionization of the silanol groups, Gd III -bound water molecules, and decreased concentration of hydronium ions. 19 This effect is less pronounced in case of the PEGylated Gd-LTL, resulting in a slightly less decrease of r 2 ( Δr 2 = 22 s –1 mM –1 ) compared to that of the non-PEGylated analogue (Figure 4b).…”

“…19 For this system (Figure 1), six water molecules in first coordination sphere of Ln III in the large cages of LTL have been determined by the measurements of luminescence lifetimes of Eu III . 17 The relaxivities showed a steep decrease from 38 to 8 s –1 mM –1 for r 1 and from 98 to 50 s –1 mM –1 for r 2 , respectively, when moving from pH 4 to 9 (7 T and 25 °C).…”

Nano assembly and encapsulation; a versatile platform for slowing the rotation of polyanionic Gd3+‐based MRI contrast agents

“…The increased per-Gd 3+ relaxivity observed for each chelate incorporated into a NAC seems to derive entirely from second-sphere contributions enhanced by slowed molecular tumbling (long τ R ). We therefore speculate that the exchange of relaxed protons from the chelate's second-sphere across the aggregate interior and silica shell to the bulk solvent occurs primarily through proton exchange (22). Whole water exchange is probably only involved in the final exchange step at the SNP shell.…”

“…We therefore speculate that the exchange of relaxed protons from the chelate’s second-sphere across the aggregate interior and silica shell to the bulk solvent occurs primarily through proton exchange. (22) Whole water exchange is probably only involved in the final exchange step across the silica shell.…”