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Radioimmunodetection of membrane type-1 matrix metalloproteinase relevant to tumor malignancy with a pre-targeting
Kohei Sano1, Takashi Temma, Yuji Kuge
1Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Abstract:
Since membrane type-1 matrix metalloproteinase (MT1-MMP) is exclusively expressed in tumors and is closely associated with metastasis and invasion, MT1-MMP is a potential target of radiotracers for the evaluation of tumor malignancy. In this study, we planned to visualize MT1-MMP in vivo by a two-step pre-targeting strategy using a streptavidin (SAv)-biotin system combined with anti-MT1-MMP monoclonal immunoglobulin (IgG) (anti-MT1-MMP monoclonal antibody (mAb)). Streptavidinylated anti-MT1-MMP mAb was synthesized by reacting biotinylated anti-MT1-MMP mAb with SAv. In the pre-targeting study, FM3A mouse breast carcinoma-implanted mice were injected with anti-MT1-MMP mAb-SAv, followed 72 h later with radioiodinated biotin, (3-[123/125I]iodobenzoyl)norbiotinamide (123/125I-IBB). Biodistribution and imaging (single photon emission computed tomography (SPECT)/CT) data were collected at several time points in the 24 h period following introduction of the tracer. The comparison groups were injected with 125I-IBB alone or with 125I-IBB pre-targeted with negative control IgG-SAv. In the pre-targeting study for MT1-MMP, within 1 h of tracer injection, rapid tumor uptake and abrupt clearance from the blood of radioactivity (2.22, 0.87% injected dose/g at 1 h) were observed. The tumor to blood (T/B) radioactivity ratios were significantly higher than those from mice dosed with the pre-targeting negative control (p<0.0001). 125I-IBB alone did not accumulate in tumors. SPECT/CT image analysis of FM3A bearing mice showed high-contrast tumor images after 3 h with minimal blood-pool activity. The present study that uses a pre-targeting method showed high T/B radioactivity ratios and clear tumor images of MT1-MMP. This imaging method may be useful for the clinical diagnosis of malignant tumors.
Insights
This study developed a novel pre-targeting imaging strategy to visualize membrane type-1 matrix metalloproteinase (MT1-MMP), a key marker for tumor metastasis. The method achieved high tumor uptake and clear imaging, showing promise for diagnosing malignant tumors.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Membrane type-1 matrix metalloproteinase (MT1-MMP) is crucial for tumor metastasis and invasion.
- MT1-MMP is a potential target for radiotracer development to assess tumor malignancy.
Purpose of the Study:
- To develop and evaluate a two-step pre-targeting strategy for in vivo visualization of MT1-MMP.
- To assess the efficacy of a streptavidin-biotin system combined with an anti-MT1-MMP antibody for tumor imaging.
Main Methods:
- Synthesized streptavidinylated anti-MT1-MMP monoclonal antibody (mAb).
- Utilized a pre-targeting approach in mice bearing FM3A breast carcinoma, involving injection of the mAb-streptavidin complex followed by radioiodinated biotin (123/125I-IBB).
- Performed biodistribution studies and single photon emission computed tomography/computed tomography (SPECT/CT) imaging.
Main Results:
- Rapid tumor uptake and clearance of radioactivity from blood were observed within 1 hour post-tracer injection.
- Significantly higher tumor-to-blood ratios were achieved compared to control groups (p<0.0001).
- SPECT/CT imaging revealed high-contrast tumor visualization with minimal background activity.
Conclusions:
- The pre-targeting imaging method demonstrated high tumor-to-blood ratios and clear visualization of MT1-MMP.
- This approach holds potential for clinical diagnosis of malignant tumors.
