A pre-targeting strategy for MR imaging of functional molecules using dendritic Gd-based contrast agents

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Bioconjugation Chemistry

Background:

• Functional molecule imaging is crucial for disease diagnosis and monitoring.
• Current imaging techniques face challenges in sensitivity and specificity.
• Pre-targeting strategies offer potential for enhanced molecular imaging.

Purpose of the Study:

• To establish a magnetic resonance imaging (MRI) protocol for sensitive and specific imaging of functional molecules.
• To utilize the streptavidin-biotin interaction for a pre-targeting strategy.
• To target membrane type-1 matrix metalloproteinase (MT1-MMP) as a model functional molecule.

Main Methods:

• Developed a biotinylated polyamidoamine dendrimer (PAMAM)-based contrast agent (Bt-PAMAM-DTPA(Gd)).
• Evaluated proton relaxivity (r1) and streptavidin affinity of the contrast agent.
• Administered streptavidin-conjugated anti-MT1-MMP monoclonal antibody (mAb) or control to tumor-bearing mice, followed by Bt-PAMAM-DTPA(Gd) and MRI.

Main Results:

• The contrast agent exhibited high proton relaxivity (r1 = 15.5 L mmol(-1) s(-1)) and enhanced affinity for streptavidin.
• Significantly higher relative tumor signals were observed in mice pre-targeted with anti-MT1-MMP mAb compared to controls (165% at 3 h).
• The pre-targeting approach demonstrated high sensitivity and specificity for in vivo imaging.

Conclusions:

• The developed pre-targeting strategy enables sensitive and specific in vivo MRI of functional molecules.
• This method holds promise for advancing molecular imaging applications.
• The streptavidin-biotin interaction is effective for pre-targeted molecular imaging.