Achievement of MT1-MMP imaging shortly after radioligand administration by pretargeting strategy with SPECT

Objectives Membrane type-1 matrix metalloproteinase (MT1-MMP) expressed in tumors is a potential target for evaluating the malignancy due to its critical role in metastasis and invasion. Thus, we aimed to achieve MT1-MMP imaging with SPECT in a few hours after the administration of a radioprobe. For the purpose, pretargeting strategy using streptavidin (SAv)-biotin system with anti-MT1-MMP monoclonal IgG (anti-MT1-MMP mAb) was adopted.

Methods Anti-MT1-MMP mAb-SAv was obtained from biotinylated anti-MT1-MMP mAb and streptavidin. FM3A breast carcinoma implanted mice were injected with anti-MT1-MMP mAb-SAv, followed 72 h later by radioiodinated biotin, ^123/125I-IBB. Biodistribution and SPECT data were obtained for 24 h. The comparison groups were injected with ¹²⁵I-IBB alone or ¹²⁵I-IBB pretargeted with negative control IgG-SAv.

Results In the pretargeting study, rapid uptake of radioactivity was observed in the tumor with a prompt clearance from the blood (Tumor; 2.36, 1.89 and 1.06 %ID/g at 3, 6 and 24 h, Blood; 0.47, 0.26 and 0.07 %ID/g at 3, 6 and 24 h). Tumor to blood ratios were significantly higher than those for negative control pretargeting study (p<0.01). ¹²⁵I-IBB alone showed negligible radioactivity in the tumor. The tumor was clearly visualized in SPECT at 3, 6 and 24 h after ¹²³I-IBB administration pretargeted with anti-MT1-MMP mAb-SAv.

Conclusions The MT1-MMP imaging was distinctly achieved in the first hours after the administration thanks to the effectiveness of the pretargeting strategy. This may provide a beneficial way to diagnose tumor malignancy in clinical settings.