ABSTRACT
A computer-controlled general purpose chemistry process control unit (CPCU) suitable for the automated production of radiochemicals has been developed. This valve-and-tubing synthesis system can be user programmed to accommodate a variety of chemical processes. In a practical demonstration of its utility, the CPCU has been configured and programmed to synthesize 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG) using aqueous [18F]fluoride ion. Using this instrument, the yield of 2-[18F]FDG from [18F]fluoride ion is 54.9% (+/- 11.2%, n = 125) corrected to EOB, after a synthesis time of 50-55 min. The average total activity produced (for runs of 5-10 microA) is 28.1 mCi/microA (+/- 5.03 mCi/microA). Thus, the amount of 2-[18F]FDG produced from a 10 microA for 1 h bombardment was 154.3 mCi (+/- 27.4 mCi). The unit has been similarly configured and programmed to synthesize 2-deoxy-2-[18F]fluoro-D-mannose (48% EOB), 3-(2'-[18F]fluoroethyl)spiperone (29% EOB), and [18F]fluoroacetate (66% EOB) from aqueous [18F]-fluoride ion, and 2-[18F]FDG from gaseous acetyl hypo[18F]fluorite (20% EOB).
Subject(s)
Computers , Fluorine Radioisotopes , Isotope Labeling/instrumentationABSTRACT
The isolated arterially perfused rabbit interventricular septum was used to study the effects of methionine sulfoximine (MSO) on 13N-labeled ammonia (13NH3) and 13N-labeled glutamine [( 13N]gln) metabolism. Tissue time-activity curves were generated from bolus injections of 13NH3 or [13N]gln delivered interarterially during control conditions and in the presence of MSO. The fraction of 13N label retained in the tissue [EF(3)] was significantly (P less than 0.01) less after a bolus of [13N]gln than 13NH3. MSO significantly (P less than 0.05) decreased the EF(3) after a bolus of 13NH3 or [13N]gln. Chemical analyses using high-pressure liquid chromatography on tissue and effluent samples obtained after bolus injections of 13NH3 and [13N]gln with or without MSO present showed the following: 1) after a bolus of 13NH3 or [13N]gln the tissue 13N label is predominantly in [13N]gln at 6 min after injection, and 2) MSO significantly decreases the synthesis of [13N]gln after an 13NH3 bolus. Thus it would appear that the glutamine synthetase reaction is primarily responsible for the retention of the 13N label from 13NH3 as [13N]gln in rabbit myocardium.
Subject(s)
Ammonia/metabolism , Glutamine/metabolism , Myocardium/metabolism , Animals , Chromatography, High Pressure Liquid , Kinetics , Male , Methionine Sulfoximine/pharmacology , Myocardium/analysis , Nitrogen Radioisotopes , RabbitsABSTRACT
L-[1-11C]leucine, suitable for the determination of cerebral protein synthesis rates in man using positron emission tomography, has been synthesized using a modified Bucherer-Strecker reaction sequence. The isolation of the pure L-amino acid isomer from the enantiomeric mixture, initially obtained using either an open or closed reaction vessel, was achieved using a D-amino acid oxidase/catalase enzyme complex immobilized on a Sepharose support. The O2 required by the D-amino acid oxidase as the hydrogen acceptor was supplied by catalase. The L-[1-11C]leucine was obtained with a radiochemical purity of greater than 99% and with a radiochemical yield of 25%. Using a remote, semiautomated synthesis system, typical production time was 30-40 min after preparation of H11CN. The use of immobilized enzymes for rapid and effective resolution of amino acid enantiomers eliminates the possibility of protein contamination and assures the production of a sterile, pyrogen-free product.
Subject(s)
Leucine , Brain/diagnostic imaging , Brain/metabolism , Carbon Radioisotopes , Chromatography , Humans , Isotope Labeling , Nerve Tissue Proteins/biosynthesis , Stereoisomerism , Tomography, Emission-ComputedABSTRACT
A simple synthetic procedure and processing system for the routine preparation of [1-(11)C]palmitic acid via carbonation of n-pentadecylmagnesium bromide with [11C]carbon dioxide is described. The key feature of this improved synthesis is the facile separation of the 11C fatty acid from the radiolabeled and unlabeled by-products of the Grignard reaction. Using this procedure and system 7.40-9.25 GBq (200-250 mCi) of [11C]CO2 was converted, after a synthesis time of 30 min, into 1.85-2.78 GBq (50-75 mCi) of pure, sterile, pyrogen-free [1-(11)C]palmitic acid suitable for human use with positron computed tomography.
Subject(s)
Carbon Radioisotopes , Isotope Labeling/methods , Palmitic Acids , Palmitic AcidABSTRACT
An approach to the design of remote semiautomated chemical processing systems has been developed and tested in more than 750 production runs. This design stresses the idea of unit operations, which allows maximum flexibility while maintaining the highest possible standards regarding safety, reliability, efficiency, and practicality. Application of this approach has resulted in the development of a simple and reliable remote semiautomated synthesis system for the routine production of [1(-11)C]2-deoxy-D-glucose. Use of this system results in the preparation of a sterile, pyrogen-free product suitable for human injection after a synthesis time of 50 min, with radiochemical purity of greater than 98% and yields (25-30%) permitting quantitative measurements using positron computed tomography.
