DISSOCIATION OF INDIUM FROM INDIUM-111-LABELED DIETHYLENE TRIAMINE PENTA-ACETIC ACID CONJUGATED NONSPECIFIC POLYCLONAL HUMAN-IMMUNOGLOBULIN-G IN INFLAMMATORY FOCI

Several investigators have reported retention of indium-111 in infectious foci after intravenous injection of In-111-labelled immunoglobulin G (IgG). With this study we intended to test the;hypothesis that, upon administration of In-111-diethylene triamine pentaacetic acid (DTPA-IgG), In-111 is retained in the infectious foci after dissociation from Igc. Therefore we measured the tissue distribution of double-labelled (111)InDTPA-IgG-(carbon-14) in rats with a focal infection and compared the results with corresponding data for DTPA-IgG-(C-14). DTPA-conjugated IgG was labelled with In-111 via citrate transchelation. In-111-DTPA-IgG and DTPA-IgG were labelled with C-14 through methylation. Highperformance 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 a Staphylococcus aureus infection of the left calf muscle were injected intravenously with 0.2 mi of a solution containing either 0.4 MBq In-111 and 30 kBq C-14 or 30 kBq C-14 labelled to 80 mu g 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 C-14 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 the C-14 plasma concentration. However, the In-111 concentration in the infectious foci remained constant over time (1.0% I.D./g) despite a decreasing concentration of In-111 in plasma. Labelling with C-14 did not influence the abscess uptake of In-111 after administration of In-111-DTPA-IgG, On the other hand, conjugation with DTPA and labelling with In111 did not influence the tissue distribution of C-14-IgG either. Assuming that C-14-IgG behaves like native IgG, our results strongly suggest that in abscesses In-111 is released from IgG with local retention of the In-111. The dissociation of In-111 from IgG provides a new explanation for retention of In-111 in sites of inflammation. This phenomenon might also be relevant to the explanation of non-specific tumour uptake of monoclonal antibodies labelled with In-111 through DTPA.