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Extracellular Aldehyde Sensing Probes for In Vivo Imaging
Yingying Ning1, Eman A Akam-Baxter1,2, Peter Caravan1
1Athinoula A. Martinos Center for Biomedical Imaging, Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, United States.
Researchers developed novel molecular probes to detect and monitor fibrosis, a key factor in many diseases. These probes target lysine aldehyde (LysAld), a biomarker elevated during fibrogenesis, enabling noninvasive imaging for diagnosis and treatment tracking.
Area of Science:
- Chemical Biology and Diagnostic Imaging
- Biomolecular Engineering
- Medical Diagnostics
Background:
- Fibrosis, characterized by excessive extracellular matrix (ECM) production, contributes to significant mortality in industrialized nations.
- Lysyl oxidases upregulate during fibrogenesis, oxidizing lysine residues in ECM proteins to form lysine aldehyde (allysine, LysAld).
- Current methods lack tools for noninvasive detection and quantification of fibrogenesis in vivo.
Purpose of the Study:
- To rationally design and validate molecular probes for the specific detection of LysAld.
- To enable noninvasive detection, staging, and treatment monitoring of fibrogenesis across various diseases.
- To establish a generalizable framework for developing molecular probes for diagnostic imaging.
Main Methods:
- Rational design of molecular probes targeting LysAld, optimizing condensation kinetics, hydrophilicity, and pharmacokinetics.
- Incorporation of electron-withdrawing groups, acidic moieties, and dual-binding ligands to enhance probe performance.
- Validation across multimodal imaging platforms including MRI, PET, and fluorescence imaging at cellular and in vivo levels.
Main Results:
- Optimized probes demonstrated enhanced sensitivity and specificity for LysAld detection in various tissues, including low-concentration systems.
- Reduced probe-adduct hydrolysis extended the imaging window, enabling specific detection in organs like the kidneys.
- Multimodal imaging validated the probes' capability for spatial-temporal insights into fibroproliferative disease dynamics.
Conclusions:
- The developed LysAld-targeting probes offer a powerful tool for noninvasive detection and monitoring of fibrogenesis.
- These probes facilitate early diagnosis, disease staging, and therapeutic response assessment in fibroproliferative diseases.
- The design strategies provide a versatile platform for developing novel molecular probes for chemical biology and diagnostic imaging.
