title: 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.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.forename: Takashi
authors.initials: T
authors.lastname: Temma
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Junko
authors.initials: J
authors.lastname: Kamihashi
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D016719:Radioimmunodetection / Q000379:methods*; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; C507096:Mmp14 protein, mouse; D053511:Matrix Metalloproteinase 14