Abstract
48
Objectives: We reported previously 99mTc- and 90Y-labeled monoclonal antibody 3H11(mAb 3H11) for diagnosis and therapy of gastric cancer. In this study, we determine the expression of 3H11 antigen on HT29 human colon cancer cells and tumor tissues, and evaluate the possibility of 111In-labeled mAb 3H11 as a radiotracer for γ imaging of colon cancer.
Methods: The expression of 3H11 antigen on HT29 cells and corresponding tumor tissues was analyzed by fluorescent staining. The Kd and Bmax were determined by saturation binding assay (125I-3H11 as a radiotracer). For 111In labeling, the bifunctional chelator CHX-A''-DTPA was conjugated to mAb 3H11. The biodistribution and γ imaging were performed in HT29 tumor-bearing nude mice.
Results: HT29 cells and xenografted tumor tissues expressed 3H11 antigen at a high level (Bmax=3.42×105/cell). The mAb 3H11 bound to the antigen with high affinity (Kd=6.09 nM). The conjugation had no effect on immunoreactivity of mAb 3H11 as determined by ELISA. The labeling yield of 111In-CHX-A''-DTPA-3H11 was 84.26%, and the RCP was more than 99% after PD-10 column purification. The radioimmunoreactive fraction was determined to be 56.0% (Lindmo method). Comparing to 111In-CHX-A''-DTPA-mIgG control, the clear images of xenografted tumors were obtained at 24 h postinjection. The tumor uptake of 111In-CHX-A''-DTPA-3H11 reached the highest with 16.71±0.78 %ID/g at 120 h p.i, and the T/NT ratios were 4.96 for blood, 30.02 for muscle, 10.29 for bone, 2.55 for kidney, 1.04 for liver, 19.42 for stomach, respectively.
Conclusions: The 3H11 antigen is expressed on HT29 colon cancer cells with high level, and this antigen may become a new promising target for diagnosis and therapy of colon cancer. 111In-CHX-A''-DTPA-3H11 shows excellent tumor targeting, so it is a good candidate for radioimmunoimaging of colon cancer.
- Society of Nuclear Medicine, Inc.