Radioimmunodetection of membrane type-1 matrix metalloproteinase relevant to tumor malignancy with a pre-targeting method.

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.

• Authors: Kohei Sano, Takashi Temma, Yuji Kuge, Takashi Kudo, Junko Kamihashi, Songji Zhao, Hideo Saji
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 33 Issue 9 Pg. 1589-95 ( 2010) ISSN: 1347-5215 [Electronic] Japan
• PMID: 20823579 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Mmp14 protein, mouse
• Matrix Metalloproteinase 14

Topics

• Animals
• Biomarkers, Tumor (analysis)
• Cell Line, Tumor
• Drug Delivery Systems (methods)
• Female
• Mammary Neoplasms, Animal (diagnosis, enzymology, pathology)
• Matrix Metalloproteinase 14 (metabolism)
• Mice
• Mice, Inbred C3H
• Radioimmunodetection (methods)
• Tissue Distribution (physiology)