Pre-targeting method improves MT1-MMP imaging for evaluating tumor malignancy
2008
561 Objectives: Since membrane type-1 matrix metalloproteinase (MT1-MMP) is exclusively expressed in tumors and closely related to metastasis and invasion, MT1-MMP should be a potential target of radiotracer for evaluating the malignancy. In this study, we planned to develop a novel MT1-MMP imaging agent based on anti-MT1-MMP monoclonal IgG (MT1-MMP mAb) combined with pre-targeting method using streptavidin-biotin (SAv-Bt) system for evaluating tumor malignancy. Methods: MT1-MMP mAb was biotinylated with NHS-LC-biotin followed by flow cytometry analysis to evaluate the immunoreactivity. SAv was radioiodinated by introducing Bt derivative, 125I-IBB. First, MT1-MMP mAb-Bt was administered to mice bearing FM3A (breast tumor), and 48 h later, 125I-IBB-SAv was injected and the biodistribution was examined for 24h. As a comparison, MT1-MMP mAb was radiolabeled with 99mTc using HYNIC as a bifunctional chelating agent followed by the biodistribution study for 24 h. Results: 99mTc-MT1-MMP mAb accumulated in the tumor in a time dependent manner (15.0%ID/g at 24 h). However, the clearance from the blood was slow, resulting in low tumor to blood (T/B) ratios throughout the study. On the other hand, in the pre-targeting study, 125I-IBB-SAv accumulated in the tumor (7.2%ID/g at 24 h) with a rapid clearance from the blood (0.8%ID/g at 24 h). Thus, the T/B ratios were significantly higher for the pre-targeting study than those for 99mTc-MT1-MMP mAb in all time points examined (99mTc-MT1-MMP mAb; 1.0, Pre-targeting; 9.0 at 24h), demonstrating the effective improvement of T/B ratios by the pre-targeting method. Conclusions: Higher T/B ratios were achieved early after the injection of 125I-IBB-SAv by the pre-targeting method, indicating that pre-targeting method using SAv-Bt system improves MT1-MMP imaging for evaluating tumor malignancy.
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