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Imaging mode | Probes | NK cell types | Time in which NK cells retain the label | Advantages | Disadvantages |
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Optical imaging | DiR | Primary NK cells, activated/expanded NK cells, or NK cell lines | The DiR NK cells can be imaged for 8 days. | Little florescence interference; high tissue penetrance; using intravital microscopy | The DiR dye would persist in the membranes even in dead cells. |
Near-infrared dye DiD | NK-92 scFv (MOCC31)-zeta cells targeted to EpCAM antigen in tumors | Long-lasting at 72 h | Easily applicable; fast; inexpensive; and provides highly sensitive noninvasive imaging in preclinical and clinical settings | The absorption and emission wavelength of the probe is less than 65 nm. Many biological tissues are capable of autofluorescence under excitation, interfering with fluorescence analysis and biological imaging of biological samples. |
ESNF | Ex vivo-expanded NK cells | Long-lasting at 72 h using concentrations as low as 0.04 μM | Do not affect NK cell purity, expression levels of surface receptors, or cytotoxic functions | — |
Quantum dots (QD705) | NK-92MI | Up to 12 days post intratumoral injection in tumors | Low toxicity; high quantum yield; color availability; good photostability; large surface-to-volume ratio; surface functionality; and small size | Weakening of nonspecific background |
Ag2 Se quantum dots (QDs) | NK-92 | — | The emission is 1350 nm, in the second near-infrared window. | — |
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PET/SPECT | C-methyl iodide | — | Half-life = 20 min for PET as well as with gamma emitting radioisotope 111in-oxine | High sensitivity for detecting labeled NK cells; high specificity | Poor spatial resolution (~1-5 mm), limited anatomic information, ionizing radiation, limited duration and number of scanning sessions |
18FDG | NK-92-scFv (FRP5)-zeta cells | 18FDG 2-4 hours to days (111In 4-7 days) | Clinically applicable; high specificity and sensitivity | Limited tracer uptake into the cells and loss of 18FDG from labeled cells |
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Magnetic resonance imaging | USPIO | NK-92 | 2-4 weeks | Without significant adverse effect on the viability of cells; FDA approved | Hardly detecting small cell populations, relative high cost, long scan times, and low specificity; limited sensitivity, limited efficient labeling efficiency |
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Optical imaging/magnetic resonance imaging | Fluorescence organic dye (Cy5.5) with magnetic nanoparticles (Fe3O4/SiO2) | NK-92MI | — | High specificity | Poor spatial resolution (~1-5 mm); limited anatomic information, ionizing radiation, limited duration and number of scanning sessions |
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