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  • 1
    ISSN: 1432-1335
    Keywords: Radioimmunoimaging ; Tumor ; Antibody ; Glycoprotein 68 ; Developing mouse brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vivo localization of a polyclonal antibody (pAb) against a glycoprotein with a molecular mass of 68 kDa (GP68), which was found in developing mouse brain, was studied in murine tumor models to evaluate potential applications of this antibody for in vivo radioimmunodetection and/or therapy of cancer. The tissue distribution of125I-labeled GP68 pAb 3 days after i.V. injection into mice bearing four different kinds of solid tumor revealed a high uptake ratio by adenocarcinoma 755 and Lewis 3LL lung cancer. In contrast, the uptake ratio was low in mice bearing Ehrlich solid tumor and sarcoma-180 (S-180). These uptake ratios accorded well with the in vitro binding activity of this antibody with the tumor cells. In an immunoscintigraphic study, adenocarcinoma 755 was successfully visualized with67Ga-labeled GP68 pAb. The results of these biodistribution and in vivo radioimmunoscintigraphic studies suggest that GP68 antibody may be applicable to the diagnosis and/or therapy of cancer.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 10 (1985), S. 29-32 
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to understand the mechanism of the accumulation of gallium citrate (Ga-67) in normal liver, an in vitro investigation system was developed using isolated rat liver cells, and various basal factors relating to 67Ga binding to normal rat liver cells were studied. In this study, the values of 67Ga binding to the liver cells increased in parallel with the number of cells; however, binding was hardly affected by higher doses of 67Ga. The binding of 67Ga to the cells was inhibited by the presence of ethylenediaminetetraacetate (EDTA) and citrate. Phosphate and bicarbonate (10-2 M) slightly inhibited 67Ga binding to the cells. The binding of 67Ga to the cells increased as the pH was decreased. These results suggest that 67Ga binding to normal rat liver cells may occur in ‘free’ gallium. Moreover, the utilization of isolated rat liver cells is useful for understanding the 67Ga accumulation mechanism in normal liver.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 13 (1987), S. 371-373 
    ISSN: 1619-7089
    Keywords: 67Ga-citrate ; Histamine ; Acute inflammation ; Paw edema ; Radioactivity ; Edema rate ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Radioactivity of 67Ga in the paw edema and the edema rate were measured after subcutaneous injection of histamine into the paw of the conscious rat. The radioactivity increased almost parallel with the edema rate following the injection of histamine. The increase in the radioactivity and edema were almost completely prevented by pretreatment with a 10 mg/kg dose of chlorpheniramine, an antihistaminic agent. A good correlation between the edema rate and the radioactivity was demonstrated. These results suggest that 67Ga-citrate is useful for monitoring the process of acute inflammation in the pharmacological evaluation of anti inflammatory drugs. Moreover, there is also a possibility that 67Ga-citrate may be useful in measuring vascular permeability.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1619-7089
    Keywords: Lectin ; Tumor ; Glycosylated antibody ; Radiopharmaceuticals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Influence on the clearance of background radioactivity from the blood was studied by using a chemically galactosylated antibody to the radiopharmaceutical. Sodium iodide I 125-labelledPisum sativum agglutinin (125I-PSA) was used as the model tumor-imaging radiopharmaceutical in this series of experiments. Rabbit (anti-PSA) immunoglobulin G (IgG) was chemically galactosylated with varying amounts of cyanomethylgalactose. Galactose concentration ranged from 11 to 17 mol/mol protein. Antibody activity was not affected by chemical galactosylation under the experimental conditions used. Blood clearance of the galactosylated anti-PSA (GAP) in normal mice was enhanced to varying degrees, depending on the degree of galactosylation; similarly, liver uptake was increased with the degree of galactosylation. Following injection of125I-PSA in normal mice, the lectin was rapidly removed from the blood by subsequent injection of GAP. Increased hepatic uptake of the complex (lectin-galactosylated antibody) via protein-carbohydrate recognition caused the pronounced decrease in the125I-PSA blood level. The effective time for125I-PSA removal was as short as 15 min. The potency was dependent on the degree of galactosylation of the antibody. In sarcoma 180 (S-180) tumorbearing mice, the capacity for blood clearance of125I-PSA was also positively correlated to the degree of galactosylation. Moreover, the variation in the delivered dose ratio of antibody to lectin proved to lead to a further increase in background clearance. As a result, especially the tumor: blood ratio was significantly improved by a single administration of chemically galactosylated antibody, as compared with the value measured in the presence of unmodified antibody. These initial studies suggest that administration of GAP may improve nuclear imaging with radiopharmaceuticals.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 9 (1984), S. 374-378 
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The binding of 67Ga to Ehrlich ascites tumor cells (ETC) was studied in vitro. Acid mucopolysaccharide (AMPS) present at the cell surface of ETC was identified as heparan sulfate (HS). The extent of 67Ga binding to ETC reached a plateau (ca. 10% of the added dose) at 1–2 h after the start of incubation. The binding was higher under neutral or alkaline conditions than under acidic conditions. Heparin and heparitinase treatment both significantly decreased the extent of 67Ga binding to ETC. Mild treatment with protease, including trypsin or papain, also decreased the binding. On the contrary, the treatment with trypsin under severe conditions markedly increased the extent of 67Ga binding to ETC. These results support the hypothesis that HS plays an important role as a 67Ga receptor in the mechanism of gallium binding to ETC.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 8 (1983), S. 52-59 
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Values of percent 67Ga binding with standard acid mucopolysaccharides (AMPS) were determined. The binding percent of 67Ga with heparan sulfate (HS) was especially high. The relation between 67Ga and HS content was investigated in liver-damaged rats. Elevated uptake of 67Ga occurred in two stages, corresponding to the early and the later stages during feeding with 2-acetylaminofluorene (AAF). Uptake of 67Ga in the liver was first observed at 5–6 weeks after the start of AAF feeding. There was a decrease at about week 7 almost to the control level, followed by a sustained increase. This changing pattern of 67Ga uptake was in good accord with that of liver HS content. A similar relation between 67Ga uptake and HS content was also observed in rat liver treated with a single dose of carbon tetrachloride (CCl4). The elevated 67Ga uptake and increased HS content induced by CCl4 were both significantly inhibited by aminoacetonitrile (AAN) or papain pretreatment. Moreover, we screened cations having a high affinity with HS from the exchangeability of 45Ca with those in 45Ca-HS complex. Fe3+ and other trivalent cations such as Al3+, La3+, Ce3+, Er3+, Sm3+, Yb3+, In3+, Ru3+, and Eu3+, and Le2+ represented strong affinity to HS. These cations also effectively decreased the 67Ga tissue distribution in normal rats. These results suggest that HS may be involved in the mechanism of 67Ga uptake in tumor and inflammatory tissues.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 9 (1984), S. 33-38 
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relationship between 67Ga uptake and iron metabolism was investigated in rat tissues. 67Ga and 59Fe(II) both accumulated in the mitochondrial-lysosomal fraction after being injected. Moreover, they both showed especially high affinity for heparan sulfate (HS) among various acid mucopolysaccharides (AMPS). When iron (ferrous citrate) was injected IV before, simultaneously with, and after 67Ga citrate IV injection, 67Ga uptake was significantly inhibited in normal rat liver in all cases. Elevated 67Ga uptake in the liver of CCl4-treated rats was also lowered to the control level by iron pretreatment. High zinc intake remarkably elevated the 67Ga uptake in rat liver. The contents of iron in the liver and liver AMPS of 0.75% zinc-fed rats were lowered in comparison with those in controls. Thus, the elevation of 67Ga uptake in the liver of zinc-fed rats might be due to the decreased of iron bound to HS.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 9 (1984), S. 51-56 
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 67Ga incorporation in the mitochondrial-lysosomal (Mt-Ly) fraction of rat liver increased sharply from 1 to 24 h after 67Ga IV injection, whereas that in the 105,000 g supernatant fraction decreased sharply from 6 to 48 h. Further, when 14C-labeled heparan sulfate (HS: biosynthesized by injection of [1-14C] glucosamine into a rat) was injected intravenously into a rat treated with Triton WR-1339, and the liver was isolated and fractionated, the radioactivity of 14C was concentrated in the lysosomal fraction. The effect of HS on 67Ga uptake in normal rat liver was also studied. On administration of 67Ga-HS complex, the peak uptake of administered radioactivity of 67Ga in rat liver occurred sooner than after the injection of 67Ga alone. The change was greatest in the Mt-Ly fraction among the subcellular fractions. Moreover, the 67Ga uptake in rat liver increased with increasing doses of HS. These results suggest that administered 67Ga may be bound to HS and that the concentration of 67Ga in lysosomes may be related to the in vivo metabolism of HS.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 10 (1985), S. 535-539 
    ISSN: 1619-7089
    Keywords: 67Ga-heparan sulfate ; Plasma membrane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of heparan sulfate (HS) in gallium citrate Ga 67 binding to rat-liver plasma membrane was investigated. HS was found to be the only acid mucopolysaccharide present on the plasma-membrane surface. The extent of 67Ga binding to the plasma membrane reached a plateau 1–2 h after the start of incubation, and binding was higher under alkaline conditions than under acidic conditions. The amount of binding increased in parallel with the protein concentration of the plasma membrane (up to 2 mg per incubation mixture). Solubilizing agents, such as bromelin and 1% Triton X-100 as well as 2 M NaCl and heparin, markedly decreased 67Ga binding, and the decrease in 67Ga binding to the plasma membrane was closely associated with the amount of HS released from the plasma-membrane surface by each solubilizing agent. On the other hand, treatment with HS markedly increased 67Ga binding to about three times the control level. These data provide further support for our previous proposal that HS plays an important role as a receptor for gallium in various tissues, including tumor cells and inflammatory tissues.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 12 (1986), S. 47-50 
    ISSN: 1619-7089
    Keywords: Gallium 67 ; Calcium 45 ; Ehrlich ascites tumor cells ; Chlorpromazine ; Ruthenium red
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to obtain more information concerning the mechanism of Gallium (67Ga) accumulation in malignant tissue, an investigation was carried out using Ehrlich ascites tumor cells. Chlorpromazine, a phospholipid stabilizer decreased the uptake of67Ga and Calcium 45 (45Ca) by the cells at low dose, but increased them at high dose. On the other hand, the uptake of both radionuclides by the cells was inhibited by ruthenium red, a Ca ATPase inhibitor in a dose dependent manner. The time course of67Ga and45Ca uptake were quite different from each other. Moreover, the subcellular distribution patterns of67Ga and45Ca were also different from each other;67Ga accumulated in the lysosomal fraction and45Ca mainly in the mitochondrial fraction. These results suggest that there may be a commonality for67Ga and45Ca uptake by the tumor cells, whereas the behaviour of these two radionuclides in the cells is dissimilar.
    Type of Medium: Electronic Resource
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