ABSTRACT
An automated, one-pot radio-synthesis module for the routine preparation of 1-[(11)C]acetoacetic acid has been developed. The enolate anion of acetone was reacted with [(11)C]CO(2) in tetrahydrofuran (THF), followed by hydrolysis and purification by ion-exchange chromatography. The total synthesis time was 18 min and radiochemical yield was 34% after decay correction. HPLC analysis showed < or =3% impurities while residual THF (< or =200 ppm) and ethanol (< or =500 ppm) were well under the tolerable limits for human studies.
Subject(s)
Acetoacetates/chemical synthesis , Acetoacetates/isolation & purification , Carbon Radioisotopes/chemistry , Carbon Radioisotopes/isolation & purification , Chromatography, Ion Exchange/methods , Isotope Labeling/methods , Robotics/methods , Acetoacetates/analysis , Acetoacetates/metabolism , Animals , Brain/metabolism , Carbon Radioisotopes/analysis , Carbon Radioisotopes/metabolism , Chromatography, Ion Exchange/instrumentation , Drug Contamination/prevention & control , Glucose/metabolism , Humans , Isotope Labeling/instrumentation , Radiopharmaceuticals/analysis , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/isolation & purification , Radiopharmaceuticals/metabolism , Robotics/instrumentationABSTRACT
Addition of both a 4-fluoro and 11beta-methoxy group onto 16alpha-[(18)F]fluoroestradiol ([(18)F]FES) yields 11beta-methoxy-4,16alpha-[16alpha-(18)F]difluoroestradiol (4F-M[(18)F]FES) with potential improved properties for positron emission tomography (PET) imaging of estrogen receptor densities in breast cancer patients. In order to provide 4F-M[(18)F]FES as a radiopharmaceutical for clinical trials, we developed an automated synthesis procedure using 3-O-methoxymethyl-11beta-methoxy-4-fluoro-16,17-O-sulfuryl-16-epiestriol as precursor. The radio synthesis involves stereoselective opening of the protected cyclic sulfone precursor via nucleophilic fluorination with [(18)F]fluoride in acetonitrile. After removal of the protecting ether and 17beta-sulphate groups by rapid hydrolysis in acidic ethanol and subsequent reversed-phase HPLC purification, the pure 4F-M[(18)F]FES was obtained as a sterile physiological saline solution in 45-50% radiochemical yield (decay corrected). The radiochemical purity of the final product was >98% and the effective specific activity (ESA) of 4F-M[(18)F]FES prepared under optimized conditions was >15,000 Ci/mmol. The total preparation time was 110+/-5 min and the product was shown to be stable for at least 6 h.
Subject(s)
Estradiol/analogs & derivatives , Radiopharmaceuticals/chemical synthesis , Receptors, Estrogen/metabolism , Automation , Chromatography, High Pressure Liquid , Estradiol/chemical synthesis , Estradiol/pharmacokinetics , Fluorine Radioisotopes/chemistry , Hydrolysis , Indicators and Reagents , Positron-Emission Tomography , Radiopharmaceuticals/pharmacokinetics , Spectrophotometry, UltravioletABSTRACT
UNLABELLED: Respiratory motion may reduce the sensitivity of (18)F-FDG PET for the detection of small pulmonary nodules close to the base of the lungs. This motion also interferes with attempts to use fused PET/CT images through software or combined PET/CT devices. This study was undertaken to assess the feasibility of respiratory gating for PET of the chest and the impact of respiratory motion on quantitative analysis. METHODS: Ten healthy subjects were enrolled in this study. Three-dimensional studies were acquired with 8 gates per respiratory cycle on a commercial PET scanner with a temperature-sensitive respiratory gating device built in-house. All scans were obtained over 42 cm of body length with 3 bed positions of 10 min each after injection of (18)F-FDG at 4.5 MBq/kg. The reconstructed images were assembled to produce gated whole-body volumes and maximum-intensity projections. The amplitude of respiratory motion of the kidneys (as a surrogate for diaphragmatic incursion) as well as the apex of the heart was measured in the coronal plane. Phantom studies were acquired to simulate the impact of respiratory motion on quantitative uptake measurements. RESULTS: The respiratory gating device produced a consistent, reliable trigger signal. All acquisitions were successful and produced reconstructed volumes with excellent image quality. Mean +/- SD motion amplitude and maximal motion amplitude values were 6.7 +/- 3.0 and 11.9 mm for the heart, 12.0 +/- 3.7 and 18.8 mm for the right kidney, and 11.1 +/- 4.8 and 17.1 mm for the left kidney, respectively. In phantom studies, the standardized uptake value for a 1-mL lesion was underestimated by 30% and 48% for the average and maximal respiratory motion values, respectively. CONCLUSION: Respiratory gating of PET of the thorax and upper abdomen is a practical and feasible approach that may improve the detection of small pulmonary nodules. Further work is planned to assess prospectively the diagnostic accuracy of this new method.
