A pre-targeting strategy for MR imaging of functional molecules using dendritic Gd-based contrast agents.
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[Purpose] : We aimed to establish a magnetic resonance imaging (MRI) protocol for the sensitive and specific imaging of functional molecules with a pre-targeting strategy utilizing the streptavidin–biotin interaction. Membrane type-1 matrix metalloproteinase (MT1-MMP) was selected as the target molecule. [Procedures] : The biotinylated polyamidoamine dendrimer (PAMAM)-based contrast agent (Bt-PAMAM-DTPA(Gd)) was prepared, and its proton relaxivity (r1) and affinity to streptavidin were evaluated. Tumor-bearing mice were pre-targeted with streptavidin-conjugated anti-MT1-MMP monoclonal antibody (mAb), streptavidin-conjugated negative control IgG, or saline and 3 days later were injected with Bt-PAMAM-DTPA(Gd) followed immediately by MRI for a period of 3 h. [Results] : High r1 (15.5 L mmol[−1] s[−1]) and 1.9-fold higher affinity than D-biotin were obtained. Significantly higher relative tumor signals were observed in mice pre-targeted with streptavidin-conjugated anti-MT1-MMP mAb (165% at 3 h vs. pre-administration) than with saline or streptavidin-conjugated negative control IgG (P < 0.0001). [Conclusions] : This pre-targeting approach can accomplish sensitive and specific in vivo MRI of functional molecules.
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