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Biomedical subjects

J S Fowler

Publications and source records attributed to J S Fowler.

At least 253 records · Page 14Linked to original sources

The effect of target-gas purity on the chemical form of F-18 during 18F-F2 production using the neon/fluorine target.

Irradiation of gas mixtures of F2/Ne (20Ne leads to d,alpha 18F) which contained percent levels ( > 0.1%) of N2, CO2, CO2, or CF4 resulted in the production of unacceptable levels of F-18-labeled NF3 and CF4 at the expense of 18F-F2. Analycical gas chromatographic methods have been devised to determine contaminant levels in the target gas as well as in the products arising from them. Commercial mixtures of 1T F2/Ne, pur F2, and neon have been analyzed for contaminants (N2, O2, CO, CO2, and CF4) and found to vary widely in the levels of these impurities from batch to batch. The N2 levels in the 1% F2/Ne mixtures varied from 0.039 to 0.49%, and the CO2 levels from 0o.018 to 0.13%. No detectable impurities were found in the neon (Research Purity), but F2 was found to contain approximately 11% CF4. Reproducibly high yields of 18F-F2 are obtained if the levels of N2, CO2, and CF4 in the final target gas mixture are < 0.01% and carrier F2 is approximately 0.1%. Hydrocarbons and CO were not detected in our gas mixtures, but would also be expected to decrease yields of 18F-F2.

Carbon Dioxide↗

A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection.

Rapid uptake of F-18 FDG was observed in a variety of transplanted and spontaneous tumors in animals. The tumor uptake reached a peak by 30 min and remained relatively constant up to 60 min, with a very slow wash-out of F-18 activity from the tumor thereafter. Tumor-to-normal tissue and tumor-to-blood ratios ranged from 2.10-9.15 and 2.61-17.82, respectively, depending on the type of tumor. A scintiscan of a seminoma in a dog showed very high uptake in the viable part and lack of uptake in the necrotic mass. Toxicological studies in mice using 1000 times human tracer dose (HTD) per wk for 3 wk and in dogs using 50 times HTD per wk for 3 wk did not show any evidence of acute or chronic toxicity.

Abscess↗

Anhydrous F-18 labeled eslemental flurine for radiopharmaceutical preparation.

Interest in fluorine- 18 as a label in radiopharmaceutical studies has led to the development of a method for the production of decicuries of anhydrous 18F-F2 using the 20Ne(d, alpha) 18F reaction. The amount of anhydrous 18F-F2 that can be removed from the target is a function of target pressure and carrier cokncentration increasing with rising target pressure and decreasing with decreasing carrier concentration. At a target pressure of 24 atmospheres and a carrier concentration of 0.1% F2, nearly 95% of the theoretical yield of fluorine- 18 produced can be removed and up to 85% delivered through a 10o-m stainless steel tube to the reaction chamber. Other functions affecting yield--including target design, target-gas handling and purity--have been addressed. Thick target yields for 14.0- and 9.4-MeV deuterons on target were measured to be 82 and 67 mCl/microA at saturation. With the BNL 60-in. cyclotron, production okf 600-800 mCl of 18F-F2 with a specific activity of approximately 10 mCi/mumole has been in effect since 1976.

Fluorine↗

A fluorimetric assay of the phosphoribosylation of 6-mercaptopurine in human blood cells.

A new fluorimetric method to assay HGPRT (hypoxanthine-guanine phosphoribosyl transferase, EC 2.4.2.8) from human red cell lysates using 6MP (6-mercaptopurine) as substrate is described. This assay is compared with an existing spectrophotometric method using hypoxanthine as substrate. Precision, sensitivity limits and kinetic differences of these assays are reported.

Erythrocytes↗

Dietary habits relating to 'wasting marmoset syndrome' (WMS).

The syndrome is a condition of poor weight gain and weakness. Changed eating habits of animals suffering from it lead to consumption of a poorly-balanced diet. By softening the diet and avoiding less nutritious foods, the eating habits can be improved and the syndrome halted. Particular attention should be paid to the palatibility of high-protein foods when weaning marmosets.

Animals↗

Urinary enzyme assays in toxicological studies in the rat and marmoset.

The relative merits of the automated, fluorimetric assay of urinary enzymes and cell exfoliation were compared with other commonly used tests for renal damage. Two types of nephrotoxic agent were used, causing crystal nephropathy and acute tubular necrosis respectively. Groups of marmosets were given one of two drugs known to cause crystal nephropathy. One agent caused intermittent increases in urinary enzyme excretion and an early increase in cell excretion which was not sustained. The second agent in contrast caused elevated cell and enzyme excretion, increasing throughout the period of administration. A nephrotoxic anti-tumour agent also caused increases in cell and enzyme excretion when given to marmosets. The early changes produced by this agent were studied using catheterised rats. Hourly samples of urine were collected and urinary beta-glycosidase excretion was found to give an early indication of renal damage, which correlated with albuminuria and glycosuria. The fluorimetric assay of urinary enzymes provides a sensitive, non-invasive test of nephrotoxicity.

Acetylglucosaminidase↗

N-acetyl-beta-d-glucosaminidase in marmoset kidney, serum and urine.

N-Acetyl-beta-D-glucosaminidase activities were determined in homogenates of marmoset kidney, in serum and in urine by using the 4-methylumbelliferyl substrate. The enzyme activity was separated into several components by DEAE-cellulose ion-exchange chromatography, starch-gel electrophoresis and isoelectric focusing. The kidney contained two major forms of the enzyme, A and B, which had similar pH optima and Km values. The A-form bound to DEAE-cellulose at pH 6.8, migrated towards the anode on starch-gel electrophoresis and had a pI of 5.0. The B-form did not bind to DEAE-cellulose at pH 6.8, remained near the origin on starch-gel electrophoresis and had a pI of 7.64. The isoenzymes also differed in heat stability, the B-form being the more stable. Serum contained B-form activity and, in addition, two intermediate forms (I1 and I2) were loosely bound to DEAE-cellulose. The serum A-form activity was less firmly bound to DEAE-cellulose than was the tissue A-form and was designated As. Serum from a pregnant marmoset contained a form which may be analogous to the human P-isoenzyme. Urine contained only a small amount of B-form activity, the majority being present in the A-form. The kidney A- and B-forms both had mol.wts. of 96000--100000 and the activity was predominantly lysosomal. Partial purification of the kidney A isoenzyme was undertaken. Immunoprecipitation studies indicated a relationship between marmoset kidney A-form and human liver A-form activity.

Acetylglucosaminidase↗

A poly[methyl-14C]methacrylate source for use in whole-body autoradiography and beta-radiography.

1. A cheap, robust, radioactive source in sheet form has been designed and constructed from commercially available material. Log-related isotopic dilutions of the source have been used to prepare a Standard Radioactive Scale. 2. The Standard Radioactive Scale has been developed as a method of internal standardization of whole-body autoradiography and its use as an aid to quantitative determination is discussed. 3. The distribution of radioactivity in the sheet source is sufficiently uniform to allow its use for high resolution radiography of thin specimens. This radiographic technique has been applied to whole body sections to demonstrate differences in quenching by tissues and to examine calcification in the rat foetus.

Acrylic Resins↗

Radiopharmaceuticals XXVII. 18F-labeled 2-deoxy-2-fluoro-d-glucose as a radiopharmaceutical for measuring regional myocardial glucose metabolism in vivo: tissue distribution and imaging studies in animals.

18F-2-Deoxy-2-fluoro-D-glucose (18FDG) is rapidly extracted by the mouse heart, and the radioactivity in heart (3-4% per organ) remains relatively constant for 2 hr post injection. The brain uptake (2-3% per organ) remained relatively constant throughout the time course of the study. Liver, lungs, kidneys, small intestine, and blood all showed a rapid clearance of radioactivity after injection of 18FDG. At 120 min the heart-to-lung ratio was 12 and heart-to-liver ratio was 32. Urinary excretion of activity was approximately 16% of the injected dose at 60 min. The uptake of radioactivity by dog heart following the intravenous administration of 18FDG was 2.8-4.1% at 60 min and 2.4% at 135 min; it was regionally distributed, the areas of highest activity being the left ventricle and the interventricular septum. The brain activity was 2.1-3.5% at 120 min, with a ratio of gray matter-to-white matter of 2-3:1. Urinary excretion in dogs was 16% and 50% of the injected dose at 60 and 135 min. The chemical form of the activity in the urine, although unidentified, was not 18F-. Cross-sectional images of the myocardium of the dog after intravenous injection of 18FDG were obtained using emission tomography.

Animals↗

Radiopharmaceuticals. 16. Halogenated dopamine analogs. Synthesis and radiolabeling of 6-iododopamine and tissue distribution studies in animals.

A simple halogenated derivative of dopamine, 6-iododopamine (1), has been synthesized using two different methods. These synthetic sequences have been applied to the radiolabeling of 1 with carbon-11, iodine-131, and iodine-123. The tissue distribution of 1 in mice, dogs, and rats was determined. The ratio of radioactivity (%/g) in the adrenal medulla-kidney in dogs increases from 3.45 at 2 h postinjection to 33.3 at 24 h postinjection. Thyroid uptakes in mice, dogs, and rats show that in vivo deiodination of 1 is not significant.

Adrenal Glands↗

Carbon-11 labeled aliphatic amines in lung uptake and metabolism studies: potential for dynamic measurements in vivo.

In order to assess the potential utility of amines labeled with short-lived nuclides as agents for lung imaging and function studies in humans, a series of aliphatic amines (C4-C10 and C13) labeled with carbon-11 (T 1/2 = 20.4 minutes), which decays by the emission of body-penetrating radiation, has been used as a model for studying some basic parameters affecting amine uptake and metabolism by the lung and other tissues in mice. The lung uptake (percentage of dose per organ) of aliphatic amines at 1 minute increased from 2.18 +/- 0.13% for butylamine to 13.33 +/- 0.84% for tridecylamine. Partition coefficients (between n-octanol and pH = 7 buffer) were measured for the C4 through C10 amines and for octanoic acid and octanenitrile. Within the amine series, the partition coefficient correlated with lung uptake. A comparison of a series of compounds all having a carbon chain length of eight but with different functional groups (--NH2, --C=N, --CO2H, --OH) showed that the amino group as well as the relatively lipophilic alkyl group were required for lung specificity. The 11C-aliphatic amines were rapidly metabolized via monoamine oxidase (ultimately to 11CO2). Non-amine metabolites in blood and lungs at 5 minutes postinjection were 95 and 50%, respectively. Pretreatment of mice with iproniazid and with pargyline decreased 11CO2 excretion, and iproniazid significantly increased the radioactivity retained by the brain, lungs and liver at 15 minutes. The rate of 11CO2 excretion depended on carbon chain length (C4 less than C5 less than C6 greater than C7 greater than C8 greater than C9 greater than C10 greater than C13).

Amines↗