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Gas phase methanol synthesis for carbon-11 radiopharmaceuticals

University of British Columbia

Carbon-11 radiopharmaceuticals are gaining an increasing importance in positron emission tomography due to their importance in diagnostic medicine. The most wide spread method of production of these radiopharmaceuticals is by methylation of an appropriate precursor with the highly reactive [¹¹C]methyl iodide. Conventional synthesis of this intermediate involves liquid phase synthesis of [¹¹C]methanol, which is the step that limits the specific activity of the final product. A catalytic gas phase methanol synthesis process was evaluated, that promises to avoid the loss of specific activity. In this procedure, [¹¹C]carbon dioxide produced in the target is first trapped and purified, then converted to [¹¹C]carbon monoxide using molybdenum and finally reduced to [¹¹C] methanol using a copper zinc oxide catalyst in the presence of hydrogen. In this study a device to trap and purify [¹¹C]carbon dioxide was developed and optimized. [¹¹C] Carbon dioxide produced in target was quantitatively trapped at -20° C on a carbon molecular sieve column and quantitatively released in less than 3.5 minutes. A reactor to convert 50 ppm carbon dioxide to carbon monoxide, based on the reaction with molybdenum, was developed. A commercially available process simulator was used to assist the optimization of operating conditions and molybdenum pretreatment methods. Under optimal conditions, carbon dioxide was converted to carbon monoxide with over 70% yield. A reactor to catalytically convert 50 ppm carbon monoxide to methanol was developed. A copper zinc oxide catalyst was prepared by a co-precipitation method. The catalyst was activated by reduction with hydrogen and passivated with compressed air prior to methanol synthesis. The effect of temperature, pressure and flowrate on the conversion of carbon monoxide to methanol were studied and results were used to create a kinetic model. This model was used to determine optimal operating conditions for this reactor and predicts 60% conversion of [¹¹C]carbon monoxide to [¹¹C]methanol. These findings suggest that gas phase [¹¹C] methanol synthesis is a viable alternative to the conventional liquid phase method, meriting further studies with carbon-11.

Text

2011-03-16

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http://hdl.handle.net/2429/32488

Chemical and Biological Engineering

University of British Columbia

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