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

Citation
D. Marshall et al., CLEARANCE OF CIRCULATING RADIO-ANTIBODIES USING STREPTAVIDIN OR 2ND ANTIBODIES IN A XENOGRAFT MODEL, British Journal of Cancer, 69(3), 1994, pp. 502-507
Citations number
27
Categorie Soggetti
Oncology
Journal title
ISSN journal
00070920
Volume
69
Issue
3
Year of publication
1994
Pages
502 - 507
Database
ISI
SICI code
0007-0920(1994)69:3<502:COCRUS>2.0.ZU;2-M
Abstract
The improved tumour to non-tumour ratios needed for effective tumour t argeting with antibodies requires that blood background radioactivity is reduced. We investigated the effect of streptavidin as a clearing a gent for I-125-labelled biotinylated anti-CEA antibodies in a human co lon carcinoma xenograft model. By comparing the biodistribution of the monoclonal antibody A5B7 with four, nine or 22 biotins per antibody m olecule, we investigated how the degree of biotinylation of the primar y radiolabelled antibody affects its clearance with streptavidin. Limi ting the degree of biotinylation limited blood clearance, whereas nine or 22 biotins per antibody molecule resulted in a 13- to 14-fold redu ction in blood radioactivity, the streptavidin-biotinylated antibody c omplexes clearing rapidly via the liver and spleen. Although a reducti on in tumour activity was also seen, a 6.6-fold improvement in the tum our to blood ratio was achieved. A comparative study of streptavidin v ersus second antibody clearance was carried out using the polyclonal a ntibody 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 bl ood radioactivity and improved tumour to blood ratios. In this case th e primary antibody was polyclonal, and therefore nonuniformity of biot inylation may affect complexation with streptavidin. Therefore, the de gree of biotinylation and type of antibody must be carefully considere d before the use of streptavidin clearance.