Effect of tumor size on monoclonal antibody uptake in a metastatic model

Abstract

We studied the effect of tumor size on monoclonal antibody (mAb) in a murine hepatic model. Intrasplenic injection of HT-29 LMM metastatic human colon cancer cell line reproducibility results in hepatic metastases formation in congenitally athymic mice. HT-29-15, a murine mAb of the IgG1 class reactive with the HT-29 LMM cell line, and BL-3, an isotype-matched control mAb, were labeled with iodine 125. Labeled mAbs were injected intravenously into mice with hepatic metastases. Animals were sacrificed on day 5, and tumor and normal tissue weighed and counted. Specific mAb uptake (percent injected dose per gram, %ID/g) by hepatic metastases (5.16 +/- 3.96) was significantly greater than nonspecific uptake (1.41 +/- 0.42) (P less than 0.001). %ID/g of tumor was dependent upon the mAb used, and was independent of tumor weight; consequently, a linear correlation between tumor weight and total uptake (%ID) for specific mAb (r = 0.88, P less than 0.0001) and nonspecific mAb (r = 0.99, P less than 0.0001) administration was demonstrated. We have shown both specific and nonspecific mAb uptake per gram of tumor to be a constant for the given mAb/tumor system and with uptake of mAb to be linearly related to tumor weight.