Development of an enzymatic pretargeting strategy for dual-modality imaging

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Radiochemistry

Background:

• Targeted cancer imaging requires specific biomarkers like HER2.
• Pretargeted imaging strategies aim to improve signal-to-noise ratio and reduce off-target effects.
• The HaloTag dehalogenase enzyme offers a unique platform for bioorthogonal chemistry and molecular conjugation.

Purpose of the Study:

• To describe a novel pretargeted imaging strategy using the HaloTag enzyme.
• To develop and evaluate HaloTag ligands for targeting HER2-expressing cells.
• To assess the dual-modality imaging capabilities of novel radiolabeled ligands.

Main Methods:

• Conjugation of HaloTag to Trastuzumab for HER2 targeting.
• Synthesis and radiolabeling of three novel HaloTag ligands.
• Evaluation of the HaloTag-Trastuzumab conjugate and radiolabeled ligands in a pretargeted imaging approach.
• Assessment of dual-modality (SPECT/optical) imaging capabilities.

Main Results:

• Successful development of a HaloTag-Trastuzumab conjugate for HER2 targeting.
• Generation of three novel radiolabeled HaloTag ligands.
• Demonstration of dual-modality imaging (SPECT/optical) for two of the developed ligands.
• The pretargeted strategy shows potential for enhanced imaging of HER2 expression.

Conclusions:

• The described HaloTag-based pretargeted imaging strategy is effective for HER2 targeting.
• Novel radiolabeled HaloTag ligands, including dual-modality agents, have been developed.
• This approach holds promise for advancing molecular imaging in oncology.