LOW-MOLECULAR-WEIGHT LANTHANIDE CONTRAST AGENTS - IN-VITRO STUDIES OFMECHANISMS OF ACTION

The MR contrast properties of a series of structurally dissimilar low molecular weight (LMW) gadolinium (Gd) and dysprosium (Dy) chelates ha ve been investigated under controlled experimental conditions in vario us in vitro test systems, Relaxation analysis (water, pH = 5.8, 37 deg rees C, .47 T) demonstrated the high dipolar relaxation efficacy of th e tested Gd chelates. The T1 and T2 relaxivities of both metal chelate series decreased with decreasing hydration number, confirming the str ong correlation between metal chelate structure and dipolar relaxivity . Susceptibility-induced T2 relaxation, commonly known as the suscepti bility effect, is modulated primarily by the magnetic susceptibility a nd 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, .41 T, 2 and 3 mM metal ion concentration) , the T2 relaxation efficacy of DyDTPA-BMA was markedly improved due t o susceptibility effects that were shown to depend on compartmentaliza tion. As the relaxation ability of GdDTPA-BMA was modulated by the dip olar interactions, compartmentalization was not a prerequisite for its T2 relaxation efficacy. In a coaxial glass system with no intercompar tmental water exchange, which eliminated the dipolar relaxation mechan ism, DyDTPA-BMA was shown to be the most efficient susceptibility agen t because of its higher magnetic susceptibility. The reported one- and two-compartment model studies have demonstrated the different mechani sm of action of LMW Gd- and Dy-based contrast agents. Gd chelates are predominantly dipolar relaxation enhancers, whereas Dy chelates are ef ficient susceptibility agents only in compartmentalized systems.