(17)O NMR Study On Water Exchange Rate of Paramagnetic Contrast Agents

ABSTRACT

PURPOSE: The water exchange rate between bulk water and bound water is an important parameter in deciding the efficiency of paramagnetic contrast agents. In this study, we evaluated the water exchange rates of various Gd-chelates using oxygen-17 NMR technique. MATERIAL AND MEHTODS The samples (Gd-DTPA, Gd-DTPA-BMA, Gd-DOTA, Gd-EOB-DTPA) were prepared by mixing 5% (17)O-enriched water (Isotech, USA). The pH of the samples was adjusted to physiological value (pH=7.0) by buffer solution. The variable temperature (17)O-NMR measurements were performed using Bruker-600 (14.1 T, 81.3 MHz) spectrometer. Bruker VT-1000 temperature control units were used to stabilize the temperature. The (17)O spin-spin relaxation times (T2) were measured using Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence with 24 echo trains. The variable temperature T2 relaxation data were then fitted into Solomon-Bloembergen equations using least square fit algorithm to estimate the water exchange times. RESULTS: From the measured (17)O-NMR relaxation rates, the determined water exchange rates at 300K are 0.42 microsecond for Gd-DTPA, 1.99 microsecond for Gd-DTPA-BMA, 0.27 microsecond for Gd-DOTA, and 0.11 microsecond for Gd-EOB-DTPA. The Gd-DTPA-BMA showed slowest exchange whereas Gd-EOB-DTPA had fastest water exchange rate. In addition, it was found that the water exchange rates of all samples had exponential temperature dependence with different decay constant. CONCLUSION: (17)O-NMR relaxation rate measurements, when combined with variable temperature technique, provide a solid tool for studying water exchange rate, which is very important in investigating the detailed mechanism of relaxation enhancement effect of the paramagnetic contrast agents.