Pre-targeted radioimmunotherapy with streptavidin-CC49 monoclonal antibody and §9§0Y-DOTA-biotin

grantor: University of TorontoIn this study pre-targeted radioimmunotherapy (RIT) of athymic mice bearing subcutaneous LS174T human colon cancer xenografts was evaluated using streptavidin-CC49 and yttrium-90 ($\sp{90}$Y)-DOTA-biotin. The biodistribution of DOTA-biotin, labeled with indium 111 ($\sp{111}$In), was first investigated in BALB/c mice to determine its suitability for pre-targeting strategies. Indium 111-DOTA-biotin was rapidly eliminated from blood and normal tissues. A dosing schedule was then determined by evaluating different time intervals between the administration of streptavidin-CC49 and DOTA-biotin and doses of DOTA-biotin in mice bearing LS174T colorectal xenografts. Comparison of 40 and 72 hour time intervals indicated that the 40 hour time interval would be the most effective for the pre-targeted RIT study. A comparison of 1, 20, 40, and 150 $\mu$g doses of DOTA-biotin indicated that 40 $\mu$g nearly achieved maximal uptake of DOTA-biotin in the tumour. Using the dosing schedule developed, the therapeutic efficacy and toxicity of pre-targeted RIT with 900 $\mu$Ci of $\sp{90}$Y-DOTA-biotin was evaluated in athymic mice bearing LS174T colorectal xenografts. Considerable suppression in tumour growth was observed in 116 treated mice. No apparent bone marrow toxicity and deterioration in health were observed in treated mice. In summary, pre-targeted RIT with streptavidin-CC49 and $\sp{90}$Y-DOTA-biotin demonstrated some promise as an effective and safe approach in the treatment of colorectal cancer.M.Sc