The effect of circulating antigen and radiolabel stability on the biodistribution of an indium labelled antibody.
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 111In 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 111In does not reduce the liver uptake of radioactivity.
Department of Surgery, University College and Middlesex School of Medicine, Sutton, Surrey, UK.
B R
BR
Davidson
J
J
Babich
H
H
Young
W
W
Waddington
G
G
Clarke
M
M
Short
P
P
Boulos
J
J
Styles
C
C
Dean
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000032:analysis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D004369:Pentetic Acid / Q000378:metabolism / Q000494:pharmacology; D016719:Radioimmunodetection; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D007205:Indium Radioisotopes; D004369:Pentetic Acid