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A Smart Self-Immobilization Magnetic Resonance Contrast Agent for Delayed Tumor Imaging In Vivo.
Zheng Huang1, Yinxing Miao1, Chunmei Lu1
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC) Nanjing University, Nanjing, 210023, China.
A novel enzyme-responsive MRI contrast agent, P-QM-Gd, covalently binds to tumor cells. This self-immobilization enhances signal and enables precise detection of small tumors, improving early cancer diagnosis.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Chemistry
Background:
- Improving magnetic resonance imaging (MRI) probe sensitivity for tumor detection is crucial.
- Current small-molecule MRI probes face challenges with tumor-specific accumulation and probe washout.
Purpose of the Study:
- To develop an enzyme-responsive, self-immobilizing small-molecule MRI probe for high-sensitivity tumor imaging.
- To enhance probe retention at the tumor site and improve MRI signal.
Main Methods:
- Designed P-QM-Gd, a probe activated by membrane-bound alkaline phosphatase (ALP).
- Enzymatic activation generates intermediates that covalently conjugate gadolinium complexes to tumor cell membranes.
- Evaluated probe performance in subcutaneous and orthotopic tumor models in mice.
Main Results:
- Enzymatic self-immobilization increased longitudinal relaxivity (r1) from 7.35 to 13.15 mM⁻¹s⁻¹.
- P-QM-Gd demonstrated rapid tumor uptake, efficient covalent labeling, and >60% MR contrast enhancement.
- Enabled precise visualization of small tumors (∼1.3 mm) up to 24 hours post-injection.
Conclusions:
- P-QM-Gd overcomes limitations of traditional MRI probes through enzymatic self-immobilization.
- Offers a promising strategy for high-sensitivity, high-spatial resolution delayed tumor MRI.
- Effective for early-stage lesion detection and improved cancer diagnosis.
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