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Imaging of blood-brain barrier damage by magnetic resonance was currently studied as to the potential of dextran-magnetite particles (DMP) for contrast enhancement. For that purpose, dextran-T10 (average molecular weight: 10.9 Kilodalton) was complexed with magnetite (Fe3O4) in ammonia. Experimental testing of the agent was made in vivo using Wistar rats with a freezing injury to the brain. DMP was i.v. injected at a dose of 90 microM Fe/kg b.w. followed by 2% Evans blue (0.6 ml). Control animals with trauma were studied without administration of DMP. Histochemical assessments were made to analyze the tissue distribution of DMP in the brain, kidney and liver after fixation in 4% formalin. MR imaging was conducted with 1.5 Tesla field strength with a circular coil 15 min after the freezing insult and administration of DMP. T1- and T2-weighted images were obtained using spin echo sequences among others. Regression analyses indicated a 50% reduction of T1 at a DMP concentration of 48 microM Fe, while for T2 only 4 microM/Fe(DMP) were sufficient for a 50% reduction. DMP was also accumulating in other organs, particularly in the Kupffer cells of the liver. Administration of DMP led to recognition of the freezing lesion as black area in agreement with macroscopical findings obtained by autopsy. In animals with a freezing lesion without administration of DMP, only T2-weighted images demonstrated a somewhat higher intensity attributable to the disruption of the blood-brain barrier. The present findings demonstrate the usefulness of DMP for contrast enhancement of lesions following disruption of the blood-brain barrier.

To study the possible application of monoclonal antibody/dextran-magnetite conjugates in specific MR imaging of brain metastases, both components of these conjugates were tested for their ability to penetrate the endothelium during conditions of local blood-brain barrier (BBB) impairment. The passage of dextran-magnetite particles (DMP) across a disrupted blood-brain barrier was studied in a freezing lesion model using electron microscopy (EM) and MR imaging. One hour after i.v. injection, focal accumulation of DMP in capillary endothelial cells within the freezing lesion was shown by EM. In parallel with this, MR imaging indicated a strong contrast enhancement in the lesion. EM observations showed that the particles were still present in the endothelial cells four and eight hours after injection. The passage of an anti-small cell lung cancer (SCLC) monoclonal antibody across the endothelium of intracerebrally xenografted human SCLC was studied using immunohistological techniques. It was found that passage across endothelial cell occurred in the tumor within four hours after injection.