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  • 1
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tissue distribution of Sc-46, Mn-54, Zn-65, In-111 and Au-195 were studied in a rat hepatoma model at various time intervals over a 96 h period. The tumor localizing properties of these isotopes were evaluated by examining their incorporation and clearance from viable and nonviable tumor tissue and determining the critical tissue ratios formed with blood and muscle. In general, the results showed greater uptake in viable than nonviable tumor tissue at early time periods (4–24 h). By 96 h, however, the activity remaining in the nonviable tumor tissue exceeded the quantity in viable tumor tissue. This trend was previously noted for Ga-67. When compared with Ga-67, only Mn-54 among the isotopes studied showed remarkably higher viable tumor/blood ratios (4–24 h, 45:1–83:1 respectively). Manganese-54 also showed highly significant accumulation in cardiac muscle with a heart/blood ratio at 4 h superior to comparable values previously reported for Cs-137 and Tl-201. It is suggested that tumor and heart imaging may be feasible utilizing radioactive manganese (Mn-51 or Mn-52) with the new positron imaging systems.
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  • 2
    ISSN: 1619-7089
    Keywords: Indium-111 ; monoclonal Fab′ ; In vivo stability human ; 111-In Fab′ excretion pattern ; Electrophoresis ; Animal distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was conducted to investigate alterations that occur in an indium/111 Fab′ of a monoclonal antibody following its in vivo administration. Patients were infused with 111 In-Fab′ of the monoclonal antibody ZCE-025. Serum and urine specimens were collected from these patients. Starting materials, serum, urine and controls samples were studied by electrophoresis. Animal distribution studies were performed in normal Balb/c mice and, in some cases, nude mice bearing a carcinoembryonic antigen (CEA)/producing human colon tumour since the antibody targets CEA. The studies indicated that the molecule circulated almost totally intact for at least 4 h and to a considerable extent for 24 h, with some evidence for in vivo fragmentation by 24 h. Evidence was also obtained suggesting the formation of a high molecular weight species in some patients. Shortly after infusion, some of the 111In in the urine appeared as the intact Fab′, but within hours the majority migrated electro-phoretically as low molecular weight species. We conclude that while the majority of the 111In-Fab′ of this particular antibody remains intact and immunoreactive following its administration, the molecule is structurally changed to some degree shortly after its infusion into humans. Since each monoclonal antibody is unique, the degree and rapidity of degradation of its Fab′ in vivo could vary markedly from the above and possibly adversely effect its utility as a radiopharmaceutical.
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  • 3
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sprague-Dawley rats were treated with varying quantities of parathyroid hormone for 1–3 days, then sacrificed at periods ranging from 1–6h after administration of 99mTc-pyrophosphate. Very little increase in bone accumulation of tracer occurred with this treatment. A small, but obvious decrease occurred in the blood levels of 99mTc-pyrophosphate and a smaller and less consistent decrease was affected in the muscle levels of the radiopharmaceutical. The overall result was an improvement in the bone/blood and bone/muscle ratios. It is suggested that the basis of the “supernormal” bone scan of hyperparathyroidism is achieved by this mechanism and that the increased bone uptake of other ions in response to parathyroid hormone is not shared by 99mTc-pyrophosphate.
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  • 4
    ISSN: 1619-7089
    Keywords: Indium-labeled IgG monoclonal antibody ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was directed toward determining the pharmacokinetic fate of an IgG2a monoclonal antibody (MoAb). The 96.5 anti-melanoma MoAb was labeled with indium-111 and indium-114m and administered to BALB/c mice. The mice receiving111In MoAb were sacrificed at 4 and 72 h, while those receiving114mIn 96.5 MoAb (50-day physical half-life) were sacrificed at 4 h and 3, 15, and 30 days. Multiple tissues were counted against a standard of the injectate and the data expressed as percent injected dose per organ and percent total dose excreted in the urine and feces. The 111 In- and114mIn-labeled MoAbs had nearly identical distribution through 72 h. Over the 30-day period 25% of the 114mIn label was excreted in the urine and 50% eliminated in the feces. All of the tissues studied showed a decrease in114mln in the 30-day period. We conclude that the metabolic products of indium-labeled MoAbs, the indium itself, or a combination of both are eliminated from the tissues over a period of several weeks and do not accumulate to a significant extent in any single site.
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  • 5
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution of cadmium-115m chloride, cobalt-57 bleomycin, selenium-75 selenite, selenium-75 selenomethionine and iodine-125 human serum albumin was investigated in rats bearing thigh implanted Morris 7777 hepatomas. Viable and nonviable tumor tissue were collected in order to determine the relative affinities of these radiopharmaceuticals for these tissues. Groups of animals were sacrificed at 4, 24, 48, 72 and 96 h following injection. Viable tumor-to-blood and muscle ratios for cadmium-115m chloride and cobalt-57 bleomycin were higher than those for gallium-67 bitrate at 4 h post-injection. The unusually high cobalt-57 bleomycin ratios for both viable and nonviable tumor were the result of very low muscle and blood values rather than high tumor uptake. Tumor-to-background ratios for iodine-125 human serum albumin, selenium-75 selenomethionine and selenium-75 selenite were inferior to those derived for cobalt-57 bleomycin or gallium-67 citrate. None of the agents included in this study compared well with gallium-67 citrate as a tumor localizing agent with the possible exception of cadmium-115m chloride and coblat-57 bleomycin at early time periods. As in most other radiopharmaceuticals studied in this model, a reversal occurred in the viable-to-nonviable tumor ratios as the time after injection increased.
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