Table 1.
Design strategies for hypoxia-targeted probes.
| Categories | Mechanism | Representative Probes | Imaging Devices | Advantages | Disadvantages | Recent Innovations | References |
|---|---|---|---|---|---|---|---|
| Physical | Direct oxygen sensing via luminescence quenching | PpyPt NPs, PtTFPP/PtOEP, Rhenium-diimine complex, Ir-BTPHSA complex, Ir-PVP, RHyLI, PtG4 | PLI, CLI | Real-time Quantitative Available to detect cyclic hypoxia |
Poor biocompatibility Low penetration depth Visible/NIR-I only |
NIR-II probes Upconversion nanoparticles | 13,14,15,72,73,74,85 |
| Biological | Enzyme-activated (NTRs, AzoRs) or Receptor-targeted (CAIX) |
HDSF, X4, CNO, 3-azo-conjugated BODIPY, Hypoxia-targeted radiotracers (18F-FMISO,18F-FAZA,18F-HX4), CAIX-800, 99mTc-PHC-102 |
FMI, PAI, PET/CT, SPECT | High specificity Good stability Easy accessibility |
Off-target activation Limited sensitivity |
Multimodal strategies | 16,17,18,19,38,42,43,68,69,70,71,106 |
| Chemical | Detection of hypoxia-relevant chemical compounds (pH, H2O2, H2S) |
Ir-D, Au@Pt-Se NPs, CD-950, MB-m-borate, QN-Naph, DNNC, AGNPs, Ir-NP, SiRho-SHD-NTR, Ir-BTPHSA | FMI, PAI, PLI | High sensitivity Good specificity High SNR Real-time and rapid response |
Cross-reactivity Complex synthesis Low penetration depth |
Dual-lock probes Ratiometric imaging Self-calibrated probe platforms | 24,25,26,27,29,30,31,32,67,72 |
NIR: near-infrared; CAIX: carbonic anhydrase IX; NTRs: nitroreductases; AzoRs: azoreductases; PLI: phosphorescence lifetime imaging; CLI: Cherenkov luminescence imaging; PAI: photoacoustic imaging; FMI: fluorescent molecular imaging; H2O2: hydrogen peroxide; H2S: hydrogen sulfide; 18F-FMISO: 18F-Fluoromisonidazole; 18F-FAZA: 18F-fluoroazomycin arabinoside; 18F-HX4: 18F-flortanidazole; PET/CT: positron emission tomography/computed tomography; SPECT: single photon emission computed tomography; SNR: signal-to-background ratio.