The T2* contrast efficacy of paramagnetic contrast agents is dependent on their magnetic properties. Vibrating sample magnetometry (VSM) and the Live Chan NMR method have been used to evaluate the influence of ligand structure on the bulk magnetic susceptibility (BMS) of low-molecular weight (LMW) lanthanide chelates. VSM was also used for the BMS assessment of LMW lanthanide chelates covalently attached to cross-linked starch particles. The ligand structure had no influence on the BMS of the gadolinium (Gd) and dysprosium (Dy) chelates. The mean BMS value of the Dy-chelates was 1.8 fold higher than that of the Gd-chelates. The holmium (Ho) DTPA-BMA chelate had a similar BMS to that of Dy-DTPA-BMA while the lowest BMS was found for europium (Eu(III)) DTPA-BMA. The covalent attachment of Gd-DTPA and Dy-DTPA to a cross-linked starch particle had no impact on their intrinsic magnetic properties. The BMS data were in good accordance with those obtained for non-particulate bound LMW Dy- and Gd-chelates. The magnetic susceptibility of the Gd-DTPA labeled particles was described by the Curie law, indicative of no magnetic interactions between Gd-DTPA molecules. The magnetic susceptibility of the Dy-DTPA labeled particles followed the Curie-Weiss law with a Curie-Weiss temperature of about-2 K, indicating magnetic interactions. The magnetic susceptibility of Dy-DTPA will, however, not be affected by such magnetic interactions at physiological temperatures.
The aim of the study was to compare the first-passage profiles of dysprosium diethylenetriamine penta-acetic acid bis(methylamide) (DTPA BMA) and the superparamagnetic iron oxide particles NSR 0430 in regions with severe and moderate cerebral ischemia. In seven rats subjected to middle cerebral artery occlusion, two dynamic MR perfusion imaging series were acquired after intravenous bolus injections of .5 mmol/kg dysprosium DTPA BMA and .06 mmolFe/kg iron oxide particles, respectively. The doses were chosen to obtain similar maximum signal change in normally perfused brain. The first-passage profiles were compared in a region of interest (ROI) in the core area with severe ischemia and in a ROI in the penumbra area of moderate ischemia. The results were compared both as the calculated mean signal intensity versus time curves for all seven rats and statistically for an estimated mean transit time (MTT) after gamma variate fitting of the calculated concentration versus time curves. The first-passage profiles for the two contrast agents were similar, both in the core area of severe ischemia and in the penumbra area of moderate ischemia. In this rat stroke model, dysprosium DTPA BMA and the superparamagnetic iron oxide particles NSR 0430 were found to be equally efficacious for the diagnosis of the perfusion deficit, but if safe for human investigations, iron oxide particles would have an advantage as equal susceptibility effect may be achieved with smaller injection volumes.
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