Synthesis and quality-control of (R)-[O-methyl-{sup 11}C]metomidate for PET[Final Programme and Abstracts Book]

Full text: The purpose of this study is to evaluate PET with the tracer {sup 11}C-metomidate as a method to identify adrenal cortical lesions. A fast and feasible synthesis and quality control method was modified and improved for this 11-{open_square}-hydroxylase inhibitor to fulfill our demands for PET. (R)-[O-methyl-{sup 11}C]metomidate was prepared by the reaction of {sup 11}C-methyl iodide with the tetrabutylammonium salt of the free acid of metomidate as precursor. The Salt was prepared by dissolving 1 mg of the acid in 100 {mu}l dichloromethane under addition of 5.2 {mu}l of 0.77 M tetrabutylammoniumhydroxide, evaporation of the solution to dryness and reconstitution of the precursor in 300 {mu}l DMF. The {sup 11}C-methyl iodide was trapped in this DMF-solution and the methylation reaction was carried out at 130 {sup o}C for 4 minutes. After addition of water the product was purified with a preparative HPLC ({mu}Bondapak C18 5 {mu}m 200 mm x 10 mm, flow 6 ml/min, wavelength 254 nm, solvent 0.3 M HCl in saline/Ethanol 65/35). The product fraction was diluted with saline and sterile filtrated (Millipore 0.22 {mu}m). Quality control was performed with analytical HPLC (C18 {mu}Bondapak, flow 1 ml/min, wavelength 254 nm, solvent 50 mM ammoniumformiate buffer pH 3.5/acetonitrile:water (50:7) 40/60), GC analysis (Poraplot Q isotherm 200 {sup o}C, split rate 10, flow 350) on residual solvents showed no remaining residues in the applicable solution and osmolality and pH were measured. The uncorrected yields of (R)-[O-methyl-{sup 11}C]metomidate were 5-10 % (corresponded to EOB, synthesis time: 40 min, specific activity 500 Ci/mmol), whereas highest losses of activity confer to the transformation of the [{sup 11}C]- carbondioxide to [{sup 11}C]-methyl iodide ({approx}50 %). The radiochemical purity is higher than 97 %, where the main impurities appear as [{sup 11}C]-methanol and [{sup 11}C]-methyl iodide. No residual solvents (DMF, Dichloromethane) could be detected in the final product, due to the complete removement by the preparative HPLC. First clinical results will be presented at the congress. PET with {sup 11}C-metomidate has the potential to be an attractive method for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from noncortical lesions. The adopted and improved synthesis method allows the fast routine support of [{sup 11}C]-metomidate for at least two patients per synthesis with a high reproducible standard. (author)