Low molecular weight lanthanide contrast agents: In vitro studies of mechanisms of action

Abstract

The MR contrast properties of a series of structurally dissimilar low molecular weight (LMW) gadolinium (Gd) and dysprosium (Dy) chelates have been investigated under controlled experimental conditions in various in vitro test systems. Relaxation analysis (water, pH = 5.8, 37 degrees C, .47 T) demonstrated the high dipolar relaxation efficacy of the tested Gd chelates. The T1 and T2 relaxivities of both metal chelate series decreased with decreasing hydration number, confirming the strong correlation between metal chelate structure and dipolar relaxivity. Susceptibility-induced T2 relaxation, commonly known as the susceptibility effect, is modulated primarily by the magnetic susceptibility and compartmentalization of the contrast agent. The influence of these parameters on the susceptibility effect of Dy diethylenetriamine penta-acetic acid bis-methylamide (DTPA-BMA) and GdDTPA-BMA was investigated in two-compartment in vitro models. In red blood cell suspensions (45% hematocrit, 37 degrees C, .47 T, 2 and 3 mM metal ion concentration), the T2 relaxation efficacy of DyDTPA-BMA was markedly improved due to susceptibility effects that were shown to depend on compartmentalization. As the relaxation ability of GdDTPA-BMA was modulated by the dipolar interactions, compartmentalization was not a prerequisite for its T2 relaxation efficacy. In a coaxial glass system with no intercompartmental water exchange, which eliminated the dipolar relaxation mechanism, DyDTPA-BMA was shown to be the most efficient susceptibility agent because of its higher magnetic susceptibility. The reported one- and two-compartment model studies have demonstrated the different mechanism of action of LMW Gd- and Dy-based contrast agents. Gd chelates are predominantly dipolar relaxation enhancers, whereas Dy chelates are efficient susceptibility agents only in compartmentalized systems.

Size-Induced Enhancement of Chemical Exchange Saturation Transfer (CEST) Contrast in Liposomes

“…7,22,28,29 T 1 is a phenomenological parameter introduced by the Bloch equations. T 1 of the liposomal system depends on the temperature, the chemical exchange rate, the chemical shift difference between the intra-and extraliposomal compartments, and the encapsulated paramagnetic ion concentrations, thus it is difficult to model accurately using basic physical principles.…”

Frequency-shift based detection of BMS contrast agents using SSFP: potential for MRA

“…If the cylinder axis is parallel to B 0 (h = 0), there is no frequency shift. Elements of the lanthanide series exhibit different magnetic properties [26][27][28]32,33]. Gadolinium is both an efficient dipolar relaxation enhancer and a susceptibility agent.…”

Gd2O(CO3)2 · H2O Particles and the Corresponding Gd2O3: Synthesis and Applications of Magnetic Resonance Contrast Agents and Template Particles for Hollow Spheres and Hybrid Composites

“…Currently, MR contrast agents are categorized into T 1 -positive agents of paramagnetic species and T 2 -negative agents of superparamagnetic particles. The paramagnetic T 1 agents include gadolinium (Gd 3þ )-, manganese (Mn 2þ )-, chromium (Cr 3þ )-, lanthanide (Ln 3þ )-, and dysprosium (Dy 3þ )-based complexes, [1][2][3][4][5][6] gadolinium-encapsulated liposomes, [7,8] and Gdbased particles. [9][10][11][12][13][14][15][16][17][18][19][20] For the Gd 3þ and Gd-based inorganic particles, the development of multifunctional particulate agents have mainly focused on bimodal MRI/optical bioimaging detection.…”