Understanding the High Longitudinal Relaxivity of Gd(DTPA)-Intercalated (Zn,Al)-Layered Double Hydroxide Nanoparticles

In this study, biocompatible gadolinium diethylenetriaminepentaacetate (Gd(DTPA))-intercalated (Zn,Al)-layered double hydroxide (LDH) nanoparticles were synthesized, characterized for Gd(DTPA) loading percentage and nanostructure, and the spin−lattice relaxation times (T1) measured to determine their suitability as a potential T1-weighted contrast agent for magnetic resonance imaging (MRI). Compared to the most commonly used contrast agent in clinical MRI (i.e., molecular Gd(DTPA)), significant increases in longitudinal relaxivity (r1) were measured for all Gd(DTPA)-intercalated nanoparticles. For a specific Zn2Al(OH)6(Cl,0.5CO3)0.56Gd(DTPA)0.086·xH2O composition, r1 was found to be 28.38 s−1mM−1, which is over 6 times the r1 of molecular Gd(DTPA). This dramatic increase in r1 is attributed to (a) the much longer rotational correlation time (τR) of nanoparticles and (b) the inherent water of LDH that forms the second-/outer-sphere in the vicinity of intercalated Gd(DTPA)2−. The latter, with an extensive hydrogen bonding network and insignificant translational motion, results in a longer mean residence lifetime (τM), which makes the contribution of second-/outer-sphere significant. Therefore, when the Gd(DTPA)2− loading percentage increases from 8.6 to 55%, the diminution of the ratio of inherent water to Gd(DTPA)2− concomitantly diminishes the contributions by second-/outer-sphere water to r1. Additionally, the modest increase in r1 with decreasing particle size (∼315−540 nm) is perhaps due to the shortening of τM. Finally, the spin−spin relaxation times (T2) of 17O, determined at various temperatures, show a negligible exchange of water molecules at room temperature. Therefore, the very high r1 of nanoparticles indicate that protons of the bulk water are still accessible to the Gd3+ centers, possibly dominated by prototropic exchange through the hydrogen bonding network