The C15O2 build-up technique to measure regional cerebral blood flow and volume of distribution of water.

A new method to measure regional CBF (rCBF) and volume of distribution of water is presented. It centres on recording the tissue build-up and retention of 15O-labelled water during the continuous inhalation of 15O-labelled carbon dioxide. Simultaneously, the arterial concentration is continuously monitored, and corrections for delay and dispersion in the recorded response are made by curve fitting.

A noninvasive positron computed tomography technique using oxygen-15--labeled water for the evaluation of neurobehavioral task batteries.

A technique is described that provides information about relative cerebral responses to differing neurobehavioral tasks in normal subjects studied with positron computed tomography and oxygen-15-labeled water. Simulation studies demonstrate that this technique is sensitive to changes in true local CBF within a physiological range and tends to underestimate relative flow changes at high flow values (greater than 30 ml min-1 100 g-1) and to overestimate these changes for flow values of less than 25 ml min-1 100 g-1. Image acquisition times of 60 s following the arrival of oxygen-15-labeled water in the brain were the most accurate for identifying such relative changes between radioisotope administrations and were not limited by statistical noise from total image counts.

Synthesis and myocardial kinetics of N-13 and C-11 labeled branched-chain L-amino acids.

Glutamate dehydrogenase (GDH), immobilized on CNBr-activated Sepharose supports, was used with N-13 ammonia to aminate alpha-ketoisocaproic acid (KIC), and alpha-ketoisovaleric acid (KIV) to produce N-13-labeled branched-chain L-amino acids with radiochemical yields ranging from 29% to 35%. From kinetic and practical considerations, pH 7.5-8.

L-[1-11C]leucine: routine synthesis by enzymatic resolution.

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 unit operations approach applied to the synthesis of [1(-11)C]2-deoxy-D-glucose for routine clinical applications.

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.

Evaluation of myocardial metabolism, with N-13- and C-11-labeled amino acids and positron computed tomography.

To evaluate the utility of labeled L-amino acids (AA) for imaging regional myocardial AA metabolism by positron computed tomography (PCT), the myocardial uptake and clearance of Ala,* Glu, Gln, Asp, Leu tagged with N-13, and of C-11-tagged Asp, and oxaloacetate (Oxal), were examined in 44 experiments at control, during ischemia, and after transaminase inhibition. The myocardial time-activity curves recorded after intracoronary tracer injection had two clearance phases (an early and a late) for all N-13 AA, and three (early, intermediate, late) for the two C-11 compounds, with significantly different clearance half-times of 18.7 +/- 8.

The varying tissue distribution of L-glutamic acid labelled at three different sites.

Methods using 5 and 6 enzymes were devised to synthesize L-[11C]glutamic acid (GA), labeled on the carboxyl group of either the alpha-(AGA) or gamma-(GGA) carbon atom. The distribution of the 11C-labeled AGA or GGA in rabbits was compared with that of L-[13N]glutamic acid. The results show that AGA was rapidly decarboxylated with loss of the 11C-label, and that GGA was also decarboxylated, but to a lesser degree.

Dependence of 13NH3 myocardial extraction and clearance on flow and metabolism.

The isolated arterially perfused rabbit interventricular septum was used to study the relationship between flow (F) and myocardial uptake and subsequent clearance of bolus injections of 13N-labeled ammonia (13NH3). Multiple 13NH3 injections were delivered to a total of 19 septa at perfusion rates (F/g) ranging from 0.2-4.

13N-labeled L-amino acids for in vivo assessment of local myocardial metabolism.

The hot cell synthesis of sterile, pyrogen-free 13N-labeled L-amino acids was accomplished by employing the appropriate immobilized enzymes on a CNBr-activated Sepharose support and using remote, semiautomated systems. The syntheses were completed 6-12 min after cyclotron production of [13N]ammonia. Myocardial time-activity curves after intracoronary injection of 13N-labeled L-amino acids in dogs were triexponential in both normal and ischemic myocardium.

Remote, semiautomated production of F-18-labeled 2-deoxy-2-fluoro-D-glucose.

A routine production system for 2-deoxy-2-[18F]fluoro-D-glucose (2-18FDG) for medical use is presented. The method involves the preparation of F-18-labeled F2 by the 20Ne(d, alpha) 18F reaction, subsequent fluorination of 3,4,6-tri-o-acetyl-D-glucal, purification, and hydrolysis of the appropriate diastereoisomer to obtain 2-18FDG. These operations are performed using a completely remote, semiautomatic system.

Lymphocyte involvement in rheumatoid arthritis. Studies during thoracic duct drainage.

Grip strength, ring size, duration of morning stiffness, and the number of tender joints improved significantly in 9 patients with severe rheumatoid arthritis during prolonged continuous removal of thoracic duct lymphocytes through a surgical fistula. There was no improvement in 4 subjects in whom surgery failed to establish satisfactory lymph drainage. Reinfusion of unlabeled or 51Cr-labeled autologous lymphocytes resulted in transient exacerbation of disease activity in 3 subjects.

Production by compact cyclotron of radiochemically pure iodine-123 as iodide for synthesis of radiodiagnostic agents.

Iodine-123-labeled radiopharmaceuticals are desirable because they give a high flux of 159-keV photons and a low radiation exposure per millicurie. Procedures suited to a compact cyclotron were developed to produce 50-mCi batches of radiochemically pure iodine-123 as iodide. Iodine-123 is separated from proton-irradiated tellurium-124 by distillation.

Experimental basis of myocardial imaging with 123I-labeled hexadecenoic acid.

Progress in myocardial perfusion imaging has been slowed by the lack or radiopharmaceuticals with suitable physical and biologic characteristics. Hexadecenoic acid, terminally labeled with 123I, partially overcomes these limitations by providing a compound that concentrates in the myocardium in proportion to relative regional blood flow and carries a gamma-emitter with desirable detection and imaging qualities. After intravenous injection in experimental animals, the clearance half-times of hexadecenoic acid for blood and myocardium are 1.

Imaging small pulmonary ischemic lesions after radioactive carbon monoxide inhalation.

A new method is described for imaging small ischemic regions in the lung immediately after a single breath of radioactive carbon monoxide (11CO). A tungsten-collimated scintillation camera is used to visualize the 0.51-MeV annihilation photons due to the 11C.

Collimation for imaging the myocardium.

Line-source response functions and modulation transfer functions (MTFs) were used to compare the resolution obtained with four myocardial-imaging agents: 129Cs, 43K, 13N-ammonia, and 81Rb contamination. When an Anger camera with pinhole collimator was used, the order of decreasing resolution was 129Cs, 43K, 13N, and 81Rb. Two techniques were employed to determine the extent to which spatial resolution could be improved.

Positron ranges obtained from biomedically important positron-emitting radionuclides.

Positron ranges were obtained experimentally for several nuclides used in scintigraphic imaging. The nuclides examined were 13C, 13N, 15O, 18F, 68Ga, and 82Rb. The results are discussed with respect to the ultimate spatial resolution obrained in a scintigraphic image.

Myocardial extraction of labeled long-chain fatty acid analogs (38509).

The single circulation myocardial extraction of terminally iodinated hexadecenoic acid (77 plus or minus 11.0%) is approximately two times the extraction of 18 carbon fatty acids (33 plus or minus 5.2%) prepared by iodination of double bonds.

The effect of azathioprine on gammaglobulin synthesis in man.

The effect of azathioprine therapy on gammaglobulin synthesis was evaluated in nine patients with rheumatic disorders. The rates of synthesis of IgG and IgM were calculated before and after 4 months of azathioprine treatment using turnover studies of radioiodinated gammaglobulins. The synthesis of IgG decreased 33.