Review Article

Overview of Strategies to Improve Therapy against Tumors Using Natural Killer Cell

Table 2

NK cell trafficking methods.

Imaging modeProbesNK cell typesTime in which NK cells retain the labelAdvantagesDisadvantages

Optical imagingDiRPrimary NK cells, activated/expanded NK cells, or NK cell linesThe DiR NK cells can be imaged for 8 days.Little florescence interference; high tissue penetrance; using intravital microscopyThe DiR dye would persist in the membranes even in dead cells.
Near-infrared dye DiDNK-92 scFv (MOCC31)-zeta cells targeted to EpCAM antigen in tumorsLong-lasting at 72 hEasily applicable; fast; inexpensive; and provides highly sensitive noninvasive imaging in preclinical and clinical settingsThe 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.
ESNFEx vivo-expanded NK cellsLong-lasting at 72 h using concentrations as low as 0.04 μMDo not affect NK cell purity, expression levels of surface receptors, or cytotoxic functions
Quantum dots (QD705)NK-92MIUp to 12 days post intratumoral injection in tumorsLow toxicity; high quantum yield; color availability; good photostability; large surface-to-volume ratio; surface functionality; and small sizeWeakening of nonspecific background
Ag2 Se quantum dots (QDs)NK-92The emission is 1350 nm, in the second near-infrared window.

PET/SPECTC-methyl iodideHalf-life = 20 min for PET as well as with gamma emitting radioisotope 111in-oxineHigh sensitivity for detecting labeled NK cells; high specificityPoor spatial resolution (~1-5 mm), limited anatomic information, ionizing radiation, limited duration and number of scanning sessions
18FDGNK-92-scFv (FRP5)-zeta cells18FDG 2-4 hours to days (111In 4-7 days)Clinically applicable; high specificity and sensitivityLimited tracer uptake into the cells and loss of 18FDG from labeled cells

Magnetic resonance imagingUSPIONK-922-4 weeksWithout significant adverse effect on the viability of cells; FDA approvedHardly detecting small cell populations, relative high cost, long scan times, and low specificity; limited sensitivity, limited efficient labeling efficiency

Optical imaging/magnetic resonance imagingFluorescence organic dye (Cy5.5) with magnetic nanoparticles (Fe3O4/SiO2)NK-92MIHigh specificityPoor spatial resolution (~1-5 mm); limited anatomic information, ionizing radiation, limited duration and number of scanning sessions