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CLEARANCE OF CIRCULATING RADIO-ANTIBODIES USING STREPTAVIDIN OR 2ND ANTIBODIES IN A XENOGRAFT MODEL

MARSHALL, D; PEDLEY, RB; BODEN, JA; BODEN, R; BEGENT, RHJ; (1994) CLEARANCE OF CIRCULATING RADIO-ANTIBODIES USING STREPTAVIDIN OR 2ND ANTIBODIES IN A XENOGRAFT MODEL. BRIT J CANCER , 69 (3) 502 - 507.

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Abstract

The improved tumour to non-tumour ratios needed for effective tumour targeting with antibodies requires that blood background radioactivity is reduced. We investigated the effect of streptavidin as a clearing agent for I-125-labelled biotinylated anti-CEA antibodies in a human colon carcinoma xenograft model. By comparing the biodistribution of the monoclonal antibody A5B7 with four, nine or 22 biotins per antibody molecule, we investigated how the degree of biotinylation of the primary radiolabelled antibody affects its clearance with streptavidin. Limiting the degree of biotinylation limited blood clearance, whereas nine or 22 biotins per antibody molecule resulted in a 13- to 14-fold reduction in blood radioactivity, the streptavidin-biotinylated antibody complexes clearing rapidly via the liver and spleen. Although a reduction in tumour activity was also seen, a 6.6-fold improvement in the tumour to blood ratio was achieved. A comparative study of streptavidin versus second antibody clearance was carried out using the polyclonal antibody PK4S biotinylated with 12 biotins per antibody molecule. This study indicated that second antibody was superior for clearance of the polyclonal antibody, resulting in a larger and faster reduction in blood radioactivity and improved tumour to blood ratios. In this case the primary antibody was polyclonal, and therefore nonuniformity of biotinylation may affect complexation with streptavidin. Therefore, the degree of biotinylation and type of antibody must be carefully considered before the use of streptavidin clearance.

Type: Article
Title: CLEARANCE OF CIRCULATING RADIO-ANTIBODIES USING STREPTAVIDIN OR 2ND ANTIBODIES IN A XENOGRAFT MODEL
Keywords: BIOTINYLATED MONOCLONAL-ANTIBODIES, RADIOLABELED ANTI-CEA, CARCINOEMBRYONIC ANTIGEN, TUMOR XENOGRAFT, CANCER, RADIOIMMUNODETECTION, ENHANCEMENT, THERAPY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: http://discovery.ucl.ac.uk/id/eprint/137373
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