Natural killer (NK) cell therapy is a promising alternative to conventional T cell-based treatments, although there is a lack of diagnostic tools to predict and evaluate therapeutic outcomes. Molecular imaging can offer several approaches to non-invasively address this issue. In this study, we systematically reviewed the literature to evaluate the state of the art of NK cell imaging and its translational potential. PubMed and Scopus databases were searched for published articles on the imaging of NK cells in humans and preclinical models. Study quality was evaluated following Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. We pooled studies as follows: Optical, magnetic resonance imaging (MRI) and nuclear medicine imaging with a total of 21 studies (n = 5, n = 8 and n = 8, respectively). Considering the limitation of comparing different imaging modalities, it appears that optical imaging (OI) of NK cells is very useful in a preclinical setting, but has the least translational potential. MRI provides high quality images without ionizing radiations with lower sensitivity. Nuclear medicine is the only imaging technique that has been applied in humans (four papers), but results were not outstanding due to a limited number of enrolled patients. At present, no technique emerged as superior over the others and more standardization is required in conducting human and animal studies.
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