A Pre-targeting Strategy for MR Imaging of Functional Molecules Using Dendritic Gd-Based Contrast Agents

Molecular Imaging and Biology - Tập 13 - Trang 1196-1203 - 2010
Kohei Sano1, Takashi Temma1, Takashi Azuma2, Ryusuke Nakai2, Michiko Narazaki3, Yuji Kuge1,4, Hideo Saji1
1Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
2Department of Medical Simulation Engineering Research Center for Nano Medical Engineering Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
3Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto, Japan
4Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan

Tóm tắt

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. 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. 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). This pre-targeting approach can accomplish sensitive and specific in vivo MRI of functional molecules.

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