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  • 1
    ISSN: 1619-7089
    Keywords: Indium-111 ; Immunoglobulin G ; Inflammation ; Infection ; Mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several investigators have reported retention of indium-111 in infectious foci after intravenous injection of111In-labelled immunoglobulin G (IgG). With this study we intended to test the hypothesis that, upon administration of111In-diethylene triamine pentaacetic acid (DTPA-IgG),111In is retained in the infectious foci after dissociation from IgG. Therefore we measured the tissue distribution of double-labelled111In-DTPA-IgG-(carbon-14) in rats with a focal infection and compared the results with corresponding data for DTPAIgG-(14C). DTPA-conjugated IgG was labelled with111In via citrate transchelation.111In-DTPA-IgG and DTPA-IgG were labelled with14C through methylation. High-performance liquid chromatography (HPLC) and instant thin-layer chromatography analysis were performed to test the in vitro stability of the labelled proteins. Young Wistar rats with aStaphylococcus aureus infection of the left calf muscle were injected intravenously with 0.2 ml of a solution containing either 0.4 MBq111In and 30 kBq14C or 30 kBq14C labelled to 80 μg IgG. Groups of five rats were sacrificed at 2, 6, 24, and 48 h. p.i. Activity uptake was determined for plasma, urine, abscess, muscle and various other tissues. Averages and standard deviations were calculated for groups of five rats. HPLC analysis was performed on plasma and urine samples taken up to 48 h p.i. The radiochemical purity of the IgG preparations was 〉95%. The labelled, preparations appeared stable in vitro. The 14C abscess activity decreased from 1.2% to 0.7% of the injected dose per gram (% I.D./g) between 2 and 48 h after injection and was linearly related to the14C plasma concentration. However, the111In concentration in the infectious foci remained constant over time (1.0% I.D./g) despite a decreasing concentration of111In in plasma. Labelling with14C did not influence the abscess uptake of111In after administration of111In-DTPA-IgG. On the other hand, conjugation with DTPA and labelling with In 111 did not influence the tissue distribution of14C-IgG either. Assuming that14C-IgG behaves like native IgG, our results strongly suggest that in abscesses 111In is released from IgG with local retention of the111In. The dissociation of111In from IgG provides a new explanation for retention of111In in sites of inflammation. This phenomenon might also be relevant to the explanation of non-specific tumour uptake of monoclonal antibodies labelled with111In through DTPA.
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  • 2
    ISSN: 1619-7089
    Keywords: Hydrazinonicotinamide ; Iminothiolane ; Immunoglobulin G ; Infection ; Inflammation ; Mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an effort to contribute to the understanding of the mechanism of uptake of technetium-99m labelled non-specific polyclonal human immunoglobulin G (hIgG) in inflammatory lesions we compared the tissue distribution of double-labelled99mTc-hydrazinonicotinamido (HYNIC) hIgG-14C and99mTc-iminothiolano hIgG-14C in groups of five Wistar rats with aStaphylococcus aureus infection of the left calf muscle between 2 h p.i. and 24 h p.i. The stability of the two double-labelled hIgG preparations was evaluated in vitro and in plasma in vivo by high-performance liquid chromatography (HPLC) analysis. At 24 h after injection of99mTc-HYNIC-hIgG-14C the abscess uptake of99mTc (1.5% ID/g±0.2% ID/g) was significantly higher (P〈0.01) than the14C uptake (1.0% ID/g±0.1% ID/g). After injection of99mTc-iminothiolano hIgG-14C no significant difference (P=0.08) was found between the abscess uptake of the two radionuclides at 24 h p.i. (99mTc: 0.8% ID/g±0.1% ID/g;14C: 0.90% ID/g±0.09% ID/g). HPLC analysis of plasma samples revealed release of99mTc from both double-labelled immunoglobulin preparations. This phenomenon was more pronounced for iminothiolano hIgG than for HYNIC hIgG (43% vs 18%). In most tissues other than abscesses significant differences were also found between the99mTc and the corresponding14C uptake. Our results demonstrate that the chemical form in which99mTc is bound to hIgG severely influences its release from hIgG and its retention in infections.
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  • 3
    ISSN: 1619-7089
    Keywords: Hydrazinonicotinamide ; Immunoglobulin G ; Infection ; Inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently a new linker — hydrazinonicotinate (HYNIC) — was introduced for labelling of proteins and peptides with technetium-99m. HYNIC and other linkers have been used for labelling of human non-specific polyclonal immunoglobulin G (hIgG) with99mTc for the detection of infections. In this study we compared the tissue distribution of three different99mTc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection withStaphylococcus aureus. We compared99mTc-HYNIC-hIgG with99mTc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the99mTc-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of99mTc. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of99mTc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%±0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%±0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of99mTc-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of99mTc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that99mTc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections.
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  • 4
    ISSN: 1619-7089
    Keywords: Scintigraphy ; Leucocytes ; Liposomes ; Nanocolloid ; Immunoglobulins ; Infection ; Inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Over the past 30 years, a wide variety of radiopharmaceuticals have been proposed for the scintigraphic detection of inflammatory and infectious disease. All radiopharmaceuticals yield a functional image of a process placed somewhere in the cascade of reactions in inflammation, this being the common pathway of response to tissue injury. This paper discusses relevant aspects of the biodistribution, in vivo kinetics and mechanisms of uptake of both clinically used and experimental radiopharmaceuticals that have been proposed for the scintigraphic detection of focal inflammation and infection.
    Type of Medium: Electronic Resource
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