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Molecular Engineering of Glycoaptamer Dual-Target Radionuclide Probes for PET/CT Imaging of Triple-Negative Breast
Deyi Zhao1,2, Yongqi Han2, Yamei Chen2
1School of Life Sciences, Shanghai University, Shanghai 200444, China.
Abstract:
Triple-negative breast cancer (TNBC) is one of the most malignant cancer types, characterized by a lack of efficient diagnostic and treatment methods in clinical practice. The development of effective targeted diagnosis and treatment for TNBC has become an important research focus. Here, we report the first proof-of-concept evidence of a glycoaptamer dual-target radionuclide probe (GDRP) for positron emission tomography/computed tomography (PET/CT) imaging of TNBC. The GDRP was created through precise molecular engineering of the aptamer AS1411, combined with three mannose ligands. The GDRP exhibited significantly increased serum stability and a high affinity for TNBC cells through a dual targeting mode. The advantages of our developed GDRP were further demonstrated by its excellent in vivo PET/CT dynamic imaging performance, featuring a long imaging window and high spatiotemporal resolution. This flexible method allows for the preparation of glycosylated functional nucleic acid molecular probes with high serum stability and tumor specificity. We anticipate that this PET/CT molecular probe will expand the development of glycoaptamer-based radioactive drugs and provides molecular tools for the clinical diagnosis of TNBC.
Insights
Researchers developed a novel glycoaptamer dual-target radionuclide probe (GDRP) for advanced imaging of triple-negative breast cancer (TNBC). This probe offers improved stability and specificity for targeted diagnosis and treatment strategies.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents significant clinical challenges due to limited diagnostic and therapeutic options.
- Development of targeted diagnostic and treatment strategies for TNBC is a critical research area.
Purpose of the Study:
- To report the first proof-of-concept for a glycoaptamer dual-target radionuclide probe (GDRP) for TNBC imaging.
- To evaluate the efficacy of GDRP in PET/CT imaging for targeted diagnosis of TNBC.
Main Methods:
- Molecular engineering of the aptamer AS1411 combined with three mannose ligands to create the GDRP.
- Assessment of GDRP's serum stability, affinity for TNBC cells via dual targeting.
- Evaluation of in vivo PET/CT dynamic imaging performance, including imaging window and spatiotemporal resolution.
Main Results:
- The developed GDRP demonstrated significantly enhanced serum stability and high affinity for TNBC cells through dual targeting.
- Excellent in vivo PET/CT imaging performance was observed, characterized by a long imaging window and high spatiotemporal resolution.
- The method enables the preparation of glycosylated functional nucleic acid probes with improved stability and tumor specificity.
Conclusions:
- The novel GDRP represents a promising molecular tool for the clinical diagnosis of TNBC.
- This glycoaptamer-based probe expands the potential for developing new glycoaptamer-based radioactive drugs.
- The findings support the advancement of targeted imaging and therapeutic strategies for triple-negative breast cancer.
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