Advances in Noninvasive Imaging of Natural Killer Cells

Natural killer (NK) cells are a critical component of the innate immune system, serving as the body's first line of defense against pathogens and malignancies. Unlike T cells, NK cells mediate cytotoxicity through distinct mechanisms, offering therapeutic potential for cancers resistant to conventional immune cell therapies. The efficacy of NK cell-based treatments heavily depends on their ability to migrate and infiltr target tissues, making the noninvasive monitoring of their in vivo behavior essential for understanding their function and optimizing therapeutic protocols. Noninvasive imaging enables real-time tracking of NK cell distribution, persistence, and functional status, providing valuable insights for predicting and evaluating treatment outcomes. Commonly used modalities include single-photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI), and optical imaging (OI), each offering unique capabilities and limitations for visualizing NK cell dynamics. This review outlines the biological functions and clinical applications of NK cells, surveys recent advances in imaging techniques designed to monitor their behavior in vivo, and compares the strengths and weaknesses of each method. Additionally, we highlight emerging imaging technologies─including ultrasound-based tracking, NIR-II imaging, and artificial intelligence─that hold promise for enhancing NK cell tracking. By bridging NK cell imaging with immunotherapy monitoring, this work aims to support the rational development of more effective cancer treatments.