Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging

Abstract

IntroductionClinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) for the detection, localization, and quantification of VivoTrax-labeled NK cells. MethodsHuman-derived NK-92 cells were labeled by co-incubation with VivoTrax for 24 hours then the excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled vs. unlabeled NK-92 cells was assessed after 4 hours of co- incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17) using bioluminescent or GFP counts. Labeled NK-92 cells at two different doses (0.5 or 1 x 106) were administered to excised mouse brains (cerebellum), tibias, and lungs then imaged by 3D preclinical MPI (MOMENTUM imager) and localized relative to fiducial markers. NK-92 cells were imaged by clinical-scale MPI under development at Magnetic Insight Inc. ResultsNK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measured effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of VivoTrax-labeled NK-92 cells, with preclinical limit of detection of 3.1 x 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, tibias, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection of a clinically relevant dose of 4 x 107 labeled NK-92 cells was demonstrated on clinical-scale MPI. ConclusionMPI can provide sensitive, quantitative, and accurate spatial information on NK cell delivery, showing its potential to resolve a significant unmet clinical need to track NK cell treatments in patients.