NMR investigation of experimental chemical induced brain tumors in rats, potential of a superparamagnetic contrast agent (MD3) to improve diagnosis

The different steps of development of chemically induced brain tumors were investigated in rats by MRI using a superparamagnetic contrast agent, magnetite-dextran nanoparticles (MD3). Sprague-Dawley strain pregnant female rats were injected intravenously with ethynitrosourea solution at the end of pregnancy. Offspring whelped by the inoculated mother were followed. MRI examinations were performed at 0.5 T. MD3 nanoparticles were injected intravenously at a dose of 5 mg Fe kg^-1 body weight 30 min before rat sacrifice. After sacrifice, histological slices were stained with hematoxylin-eosin. Relaxation times were measured at 40 MHz and 37°. MD3 nanoparticles act differently according to the step of the tumor development. Before tumor appearance, at a step characterized by the presence of abnormal cell clusters, relaxation time T2 increased significantly. The T2-weighted image showed a small increase in signal intensity in the lesion. Image contrast was improved by MD3 nanoparticles injection because of the decrease in healthy tissue signal intensity. The Tl-weighted image did not provide any additional information. In presence of a minute tumor, relaxation times decreased in tumor but increased in surrounding tissue. The Tl-weighted image showed a hypersignal on the border of an hyposignal. T2-weighted image showed a hypersignal in the same area. Signal intensity was not modified after MD3 nanoparticles injection. When new vascular capillaries developed in the tumor, MD3 nanoparticles cross into the cerebral parenchyma. Transmission electron microscopy showed magnetite crystals in this specific area on cytoplasm vesicles of glial cells and in tumor-specific membrane arrangements. On T2-weighted image, the hypersignal consisted of a well defined part and a second more fuzzy part, its signal being extinguished after MD3 nanoparticles injection. Necrotic areas and edema can be discriminated. The use of such a superparamagnetic contrast agent would be helpful in early detection of tumor development and in improving distinction of tumor mass from its vascular environment in patients. © 1998 Elsevier Science B.V. All rights reserved.     

An iron-based T 1 contrast agent made of iron-phosphate complexes: In vitro and in vivo studies

A new iron-based T ₁ contrast agent consisting of a complex of iron ions coordinated to phosphate and amine ligands (Fe_(phos) in short) has been characterized by spectroscopic and magnetic measurements. NMR relaxation studies showed r ₁ values to be dependent on the phosphate salt concentration, K₂HPO₄, present in the medium. r ₁ reaches a maximum value of 2.5 mM^?1 s^?1 for measurements carried out at 7 T and 298 K. ³¹P MRS, Mössbauer spectroscopy and magnetic measurements of Fe_(phos) solutions suggest paramagnetic Fe³⁺ ions present in the studied iron–phosphate complex. In vitro and in vivo toxicity experiments with C6 cells and CD1 mice, respectively, demonstrated lack of toxicity for Fe_(phos) at the highest dose tested in the MRI experiments (12 mM iron for C6 cells and 0.32 mmol iron/kg for mice). Finally, T ₁ weighted images of brain tumours in mice have shown positive contrast enhancement of Fe_(phos) for tumour afflicted regions in the brain.