Dissertation Abstract

Investigation of Iron(III) Tironate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent.

Iron(III) tironate, a new and stable complex, potentially useful as a magnetic resonance imaging contrast agent, was prepared, and its toxicity and magnetic resonance (MR) imaging properties were evaluated. In tests of acute and subacute toxicity, no deaths resulted from intravenous injections of 0.05, 0.10, and 0.15 mmol/kg of iron(III) tironate in Sprague-Dawley and Fisher 344 rats, but there was a 100% mortality when the doses were 0.20 and 0.30 mmol/ kg. No abnormal behavior was noted in the surviving animals. Ultraviolet-visible spectroscopy of the urine of rats receiving 0.05, 0.10, and 0.20 mmol/kg revealed no free iron(III) tironate, suggesting in-vivo stability, with 97-100% of the compound (at the 0.05 and 0.10 mmol/kg dosages) being recovered in the urine 48 h post-injection. On MR animal imaging, using a standardized imaging protocol, there was a significant visual increase in contrast enhancement of the kidneys and a minor increase in enhancement of the liver and bowel on T$„sb1$-weighted images when compared to controls. Additionally, T$„sb1$ relaxation times were decreased, especially in the kidneys. When compared to Gd-DTPA the iron contrast agent provided similar image enhancement. The results of the animal MR studies were augmented by phantom MRI studies. These findings suggest that further

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