The effect of circulating antigen and radiolabel stability on the biodistribution of an indium labelled antibody

Abstract

Summary This study has investigated two of the main problems with radiolabelled antibody imaging, the formation of circulating immune complexes (I.C.) and the non specific binding of radiolabel to the antibody molecule.Patients undergoing immunoscintigraphy with "'In labelled monoclonal antibody ICR2 were divided into three groups who received either the radiolabelled antibody alone (control, n = 12), the radiolabelled antibody which was incubated with the chelating agent diethylene triamine pentacetic acid (DTPA) prior to size exclusion chromatography (n = 6) or whose injectate was treated with DTPA and cold MAb administered intravenously prior to radiolabelled MAb administration (n = 6). Radiolabelled antibody uptake in abdominal organs was measured by region of interest analysis using a gamma camera with online computer and that in tumour and normal tissues by gamma well counting of biopsies. Circulating antigen and immune complex was measured by high pressure liquid chromatography (HPLC).The sensitivity of tumour imaging and the tumour uptake of radiolabelled antibody was not significantly different between the groups. Patients with high circulating antigen levels developed high levels of circulating immune complex but also had high tumour uptakes of radiolabelled antibody. Administration of cold MAb increased the splenic, but did not effect the tumour uptake of radiolabelled antibody and only minimally reduced levels of circulating immune complex. Chelate administration reduced the urinary excretion of radioactivity but increased the liver uptake of radioactivity.These results have shown that successful antibody imaging can be carried out despite high levels of circulating antigen, that large doses of unlabelled antibody are required to prevent immune complex formation and that removal of non specifically bound "'In does not reduce the liver uptake of radioactivity.

Selective Antitumor Effect of Thioether-Linked Immunotoxins Composed of Gelonin and Monoclonal Antibody to Alpha-Fetoprotein or Its F(ab^/)Fragment

“…However, Koji et al [7] and Ishii et al [8] reported that anti-AFP antibodies were deliv ered to hepatoma cells in spite of the presence of enough serum AFP to neutralize them. Similar results were reported with systems using anti-CEA MoAb [4] and other MoAbs [3,9], indicating that circulating antigen did not always interfere with tumor targeting. These results suggest that even circulating an tigens such as AFP or CEA can be suitable tar get candidates for tumor targeting when the selection of MoAbs against them is well op timized as targeting carriers.…”

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

“…The high level of urinary excretion of "'In at 2 h p.i., which seems higher than that of l4C (difference not sig nificant), seems to support the suggestion by Davidson and co-workers that a part of the "'In is not tightly bound to the IgG [15]. In vitro, however, '" In-DTPAIgG-('4C) appears to be rather stable (cf.…”

Different biodistribution of 99mTc-labelled chimeric mouse-human monoclonal antibody between athymic mice model and human

“…Lack of immunodetection and complications associated With MAb cross-reactive with circulating cells had been reported (Diliman et al. 1984 labelled MAb which formed a circulating immune complex have been reported (Hnatowich et al, 1987;Davidson et al, 1991). In the present study, increased liver uptake of radiolabelled MAb was noted as in the previous studies, although the pharmacokinetics were different and imaging was not successful.…”