Dynamics of monoclonal antibody distribution and prolonged tumour localisation in nude mice bearing a human CEA-producing colon carcinoma xenograft

Abstract

A new monoclonal anti-CEA antibody (1H12) has been raised which has localising characteristics in a human colon tumour xenograft which could make it suitable for human immuno-radiotherapy. The amount of 1H12 localising in tumour reached about 5% of the injected dose by 7 hours. This rate appeared to be related to the concentration of 1H12 in the blood pool since non-excretory normal organs such as colon and stomach accumulated similar amounts up to 4 hours. Whereas 1H12 was lost from normal organs after 4 hours, the amount in the tumour continued to increase slightly reaching a maximum concentration of 6.5% of the injected dose by day 9. Prolonged retention of 1H12 in tumour enabled increasing tumour: normal tissue ratios to be attained during the residence time of the antibody thus providing scope for maximising the dose of radiation delivered to tumour cells. Preliminary dose escalation showed that up to 500 micrograms of 1H12 could be administered with increasing concentrations of antibody localising in tumour. Saturation of the tumour site was evident in only one mouse where 1.09 micrograms of 1H12 actually localised--equivalent to 60 micrograms per gram of tumour.