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

作者：Sano Kohei; Temma Takashi; Azuma Takashi; Nakai Ryusuke; Narazaki Michiko; Kuge Yuji; Saji Hideo^*

来源：Molecular Imaging and Biology, 2011, 13(6): 1196-1203.

DOI：10.1007/s11307-010-0463-1

• Pre-targeting
• Polyamidoamine dendrimer (PAMAM)
• Membrane type-1 matrix metalloproteinase
• Magnetic resonance imaging

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.

• 出版日期2011-12