Dissociation of indium from indium-111-labelled diethylene triamine penta-acetic acid conjugated non-specific polyclonal human immunoglobulin G in inflammatory foci

Autor: J.W.M. van der Meer, Wim J.G. Oyen, E.B. Koenders, Roland A. M. J. Claessens, O.C. Boerman, F.H.M. Corstens, George F. Borm
Rok vydání: 1995
Předmět:
Male
medicine.drug_class
Development and evaluation of radiopharmaceuticals labeled with short living radionuclides for detection of inflammatory foci
Urine
Monoclonal antibody
Immunoglobulin E
High-performance liquid chromatography
Immunoglobulin G
Febris e causa ignota
medicine
Animals
Radiology
Nuclear Medicine and imaging
Tissue Distribution
Carbon Radioisotopes
Rats
Wistar
Radionuclide Imaging
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)
Chromatography
High Pressure Liquid
Fever of unknown origin
biology
Chemistry
Indium Radioisotopes
General Medicine
Pentetic Acid
Staphylococcal Infections
Molecular biology
In vitro
Abscess
Rats
Polyclonal antibodies
Immunology
biology.protein
Antibody
Ontwikkeling en evaluatie van radiofarmaca gemarkeerd met kort-levende radionucliden ten behoeve van detectie van ontstekingsprocessen
Zdroj: European Journal of Nuclear Medicine, 22, 3, pp. 212-219
European Journal of Nuclear Medicine, 22, 212-219
European Journal of Nuclear Medicine, 22, pp. 212-219
ISSN: 0340-6997
Popis: 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.
Databáze: OpenAIRE
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