Development of a Novel HER2-Targeted Peptide Probe for Dual-Modal Imaging of Tumors

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Cancer Diagnostics

Background:

• Human epidermal growth factor receptor 2 (HER2) is a key target for cancer diagnosis and therapy.
• Dual-modal imaging probes combining near-infrared window II (NIR-II) and positron emission tomography (PET) are crucial for precise HER2-positive tumor detection.
• Development of targeted probes is essential for advancing theranostic applications in oncology.

Purpose of the Study:

• To design and evaluate novel HER2-targeted peptide probes for dual-modal NIR-II and PET imaging.
• To assess the tumor imaging performance of three distinct probes (DOTA-ZC01-ICG, DOTA-KSP-ICG, DOTA-ZC02-ICG) in vivo.
• To establish a new molecular scaffold for developing HER2-targeted theranostic agents.

Main Methods:

• Design and synthesis of three HER2-targeted peptide probes modified with indocyanine green (ICG) and DOTA.
• In vivo NIR-II imaging in SKOV3 tumor-bearing mice to evaluate tumor targeting and imaging performance.
• Radiolabeling of the optimal probe with Gallium-68 (⁶⁸Ga) for PET imaging and subsequent biodistribution studies.

Main Results:

• DOTA-ZC02-ICG demonstrated superior tumor imaging performance in NIR-II scans, achieving the highest tumor-to-noise (T/N) ratio of 5.4 at 4 hours post-injection.
• ⁶⁸Ga-labeled DOTA-ZC02-ICG ([⁶⁸Ga]-DOTA-ZC02-ICG) clearly delineated tumors in PET imaging within 2 hours post-injection, with a peak uptake of 1.9 %ID/g at 0.5 hours.
• Tumor uptake was significantly reduced in blocking studies, confirming the specificity of the probe for HER2.

Conclusions:

• DOTA-ZC02-ICG is a highly effective dual-modal imaging probe for HER2-positive tumors, offering excellent performance in both NIR-II and PET imaging.
• The developed molecular scaffold provides a promising platform for creating advanced HER2-targeted theranostic agents.
• This study highlights a significant advancement in molecular imaging techniques for cancer diagnosis and potential therapeutic strategies.