Near-Infrared I fluorescent dyes refer to fluorescent dyes with emission wavelengths in the 700–900 nm range. Compared to visible light (400–700 nm), fluorescence imaging in this波段 offers deeper tissue penetration depth and lower autofluorescence background, making it the most widely used near-infrared window for in vivo imaging. Several NIR-I dyes (such as ICG) have received FDA/EMA approval and have entered clinical use.
I. Physical Basis and Advantages of the NIR-I Window
| Characteristic | Visible Light (400–700 nm) | NIR-I (700–900 nm) | Improvement |
| Tissue Penetration Depth | <1 mm | 1–5 mm | 3–5 times improvement |
| Autofluorescence | High (hemoglobin, melanin, water) | Low | Significantly improved signal-to-noise ratio |
| Scattering | High | Moderate | Improved resolution |
| Primary Absorbers | Hemoglobin, melanin | Water, lipids (weak absorption) | Reduced absorption interference |
| Clinical Instrument Availability | High (microscopes, endoscopes) | Moderate to High (IVIS, Pearl, endoscopes) | Strong translatability |
Physical Principle: In the 700–900 nm range, the molar extinction coefficients of hemoglobin and melanin decrease significantly, while the water absorption peak has not yet appeared (water absorption peak >970 nm), creating the so-called "optical transparency window".
II.Applications of NIR-I Dyes in Live Imaging
1. Vascular and Lymphatic Angiography
ICG angiography is the most mature clinical application of NIR-I imaging:
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Fundus Angiography: Assessing retinal blood flow perfusion; diagnosing macular degeneration and diabetic retinopathy
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Lymphography: Sentinel lymph node mapping for surgical navigation in breast cancer and melanoma
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Tissue Perfusion Assessment: Evaluating blood supply after flap surgery or intestinal anastomosis
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Cerebrovascular Imaging: Imaging cerebral cortex blood vessels in mice; assessing cerebral hemodynamics
Operational Note: ICG binds to plasma proteins after intravenous injection, remaining in blood vessels with a half-life of approximately 3–5 minutes.
2. Tumor-Targeted Imaging
By conjugating NIR-I dyes to antibodies, peptides, or small molecule ligands, tumor-specific imaging can be achieved:
| Target | Conjugate | Dye | Application |
|---|---|---|---|
| HER2 | Trastuzumab | IRDye 800CW | Breast cancer imaging |
| PD-L1 | Anti-PD-L1 antibody | ICG / IRDye 800CW | Immunotherapy response prediction |
| EGFR | Cetuximab | IRDye 800CW | Head and neck cancer, colorectal cancer imaging |
| PSMA | PSMA ligand | IRDye 800CW | Prostate cancer imaging |
| Integrin αvβ3 | RGD peptide | Cy7 | Tumor angiogenesis imaging |
Clinical Progress: Multiple NIR-I targeted probes have entered clinical trials (e.g., probes for tumor surgical navigation).
3. Liver Function Assessment
ICG is metabolized by the liver and excreted via bile; its clearance rate reflects liver function status:
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Indocyanine Green Clearance Test: Assessing liver reserve function before cirrhosis or hepatectomy
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Postoperative Liver Function Monitoring: Evaluating early graft function after liver transplantation
4. Inflammation and Disease Imaging
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Arthritis Imaging: ICG accumulates in inflamed joints due to increased vascular permeability
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Atherosclerosis: NIR-I dyes label macrophages to assess plaque inflammation
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Ischemia-Reperfusion Injury: Assessing tissue perfusion recovery
5. Surgical Navigation
NIR-I imaging has significant value in intraoperative navigation:
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Tumor Boundary Identification: Helping surgeons distinguish tumor from normal tissue
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Sentinel Lymph Node Mapping: Avoiding unnecessary lymph node dissection
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Bile Duct Visualization: Preventing bile duct injury (ICG cholangiography)
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Nerve Identification: Some NIR-I dyes can label peripheral nerves
III. Advantages and Limitations of NIR-I Dyes
| Dimension | Advantages | Limitations |
|---|---|---|
| Penetration Depth | 1–5 mm, superior to visible light; sufficient for superficial tissue and intraoperative imaging | Not suitable for deep organs (e.g., deep liver, deep brain) |
| Autofluorescence | Low, good signal-to-noise ratio | Some autofluorescence remains (especially in liver and kidneys) |
| Clinical Translation | ICG and others FDA/EMA approved; high instrument availability | Most targeted probes still in clinical trials |
| Imaging Instruments | High availability of IVIS, Pearl, endoscopes | Limited resolution compared to NIR-II |
| Dye Stability | Most NIR-I dyes have good photostability | ICG has poor stability in aqueous solution; prone to aggregation |
| Multiplexing Capability | Can be combined with visible and NIR-II dyes | Significant spectral overlap among multicolor NIR-I dyes |
IV.Selection Guide
| Application Scenario | Recommended Dyes | Rationale |
|---|---|---|
| Angiography, Intraoperative Navigation | ICG | Clinical gold standard; FDA/EMA approved; widely available instruments |
| Tumor-Targeted Imaging | IRDye 800CW, Cy7 | High photostability, high conjugation efficiency, numerous clinical trials |
| Cell Tracing (In Vivo) | DiR | Lipid-soluble; stable membrane labeling; NIR-I penetration |
| Multicolor NIR-I Imaging | Cy7 + Alexa Fluor 750 | Good spectral separation |
| Combined NIR-I and NIR-II Imaging | ICG (NIR-I) + NIR-II dyes | Multi-window imaging; complementary information |
| Liver and Kidney Function Assessment | ICG | Clinical standard method; clearance rate reflects function |
| Lymphatic Imaging | ICG | Gold standard for sentinel lymph node mapping |
V. Future Trends
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Accelerated Clinical Translation of NIR-I Targeted Probes: Multiple tumor-targeted NIR-I probes have entered clinical trials for surgical navigation and diagnostic imaging
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NIR-I/NIR-II Multi-Window Imaging: Combined use of NIR-I and NIR-II dyes enables multi-scale imaging from superficial to deep tissues
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Smart Responsive NIR-I Probes: Development of activatable NIR-I probes responsive to pH, enzymes, and reactive oxygen species to reduce background signal
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Development of Novel NIR-I Dyes: Improving photostability, quantum yield, and biocompatibility to overcome ICG limitations (poor stability in aqueous solution)
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Integration of NIR-I with Photothermal Therapy: NIR-I dyes with both fluorescence imaging and photothermal conversion capabilities enable theranostic applications
艳 李
