Sehl Olivia C, Yang Yanwen, Anjier Ariana R, Nevozhay Dmitry, Cheng Donghang, Guo Kelvin, Fellows Benjamin, Mohtasebzadeh Abdul Rahman, Mason Erica E, Sanders Toby, Kim Petrina, Trease David, Koul Dimpy, Goodwill Patrick W, Sokolov Konstantin, Wintermark Max, Gordon Nancy, Greve Joan M, Gopalakrishnan Vidya
Magnetic Insight Inc, 2020 N Loop Rd, Alameda, CA, 94502, USA.
Department of Pediatrics Research, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, USA.
Mol Imaging Biol. 2025 Feb;27(1):78-88. doi: 10.1007/s11307-024-01969-z. Epub 2024 Dec 9.
Clinical 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) may have applications for the quantitative detection of NK cells.
Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 10) were administered to excised mouse brains (cerebellum), fibulas, and lungs then imaged by 3D preclinical MPI (MOMENTUM™) for detection relative to fiducial markers. NK-92 cells were also imaged by clinical-scale MPI under development at Magnetic Insight Inc.
NK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measurable effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of labeled NK-92 cells, with preclinical limit of detection of 3.1 × 10 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, fibulas, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection on a clinical-scale MPI scanner was demonstrated using 4 × 10 labeled NK-92 cells, which is in the range of NK cell doses administered in our previous clinical trial.
MPI can provide sensitive, quantitative, and accurate spatial information on NK cells soon after delivery, showing initial promise to address a significant unmet clinical need to track NK cell fate in patients.
自然杀伤（NK）细胞免疫疗法正在髓母细胞瘤和骨肉瘤的临床治疗中应用，然而目前对于给药后细胞命运的反馈很少。我们提出磁性粒子成像（MPI）可能在NK细胞的定量检测中具有应用价值。
将人源NK-92细胞与氧化铁纳米颗粒（VivoTrax™）共同孵育24小时进行标记，然后通过离心洗涤去除过量的纳米颗粒。在与髓母细胞瘤细胞（DAOY）或骨肉瘤细胞（LM7或OS17）共同孵育4小时后，评估标记的和未标记的NK-92细胞的细胞溶解活性。将两种不同剂量（0.5或1×10）的标记NK-92细胞注射到切除的小鼠脑（小脑）、腓骨和肺中，然后通过3D临床前MPI（MOMENTUM™）成像以相对于基准标记进行检测。NK-92细胞也通过Magnetic Insight Inc.正在开发的临床规模MPI进行成像。
NK-92细胞平均每个细胞标记有3.17 pg铁，对细胞活力或针对3种肿瘤细胞系的细胞溶解活性没有可测量的影响。MPI信号与标记的NK-92细胞数量直接呈定量关系，在MOMENTUM成像仪上临床前检测限为3.1×10个细胞。使用临床前扫描仪，标记的NK-92细胞可以在立体定向注射坐标的<1毫米范围内准确地定位在小鼠脑、腓骨和肺中。使用4×10个标记的NK-92细胞证明了在临床规模MPI扫描仪上进行检测的可行性，这在我们之前的临床试验中施用的NK细胞剂量范围内。
MPI可以在给药后不久提供关于NK细胞的敏感、定量和准确的空间信息，显示出初步的前景，以满足在患者中追踪NK细胞命运这一重大未满足的临床需求。
