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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
In vivo imaging of nanoparticle-labeled CAR T cells
Louise Kiru1, Aimen Zlitni1, Aidan Michael Tousley2
1Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 94305.
Abstract:
Metastatic osteosarcoma has a poor prognosis with a 2-y, event-free survival rate of ∼15 to 20%, highlighting the need for the advancement of efficacious therapeutics. Chimeric antigen receptor (CAR) T-cell therapy is a potent strategy for eliminating tumors by harnessing the immune system. However, clinical trials with CAR T cells in solid tumors have encountered significant challenges and have not yet demonstrated convincing evidence of efficacy for a large number of patients. A major bottleneck for the success of CAR T-cell therapy is our inability to monitor the accumulation of the CAR T cells in the tumor with clinical-imaging techniques. To address this, we developed a clinically translatable approach for labeling CAR T cells with iron oxide nanoparticles, which enabled the noninvasive detection of the iron-labeled T cells with magnetic resonance imaging (MRI), photoacoustic imaging (PAT), and magnetic particle imaging (MPI). Using a custom-made microfluidics device for T-cell labeling by mechanoporation, we achieved significant nanoparticle uptake in the CAR T cells, while preserving T-cell proliferation, viability, and function. Multimodal MRI, PAT, and MPI demonstrated homing of the T cells to osteosarcomas and off-target sites in animals administered with T cells labeled with the iron oxide nanoparticles, while T cells were not visualized in animals infused with unlabeled cells. This study details the successful labeling of CAR T cells with ferumoxytol, thereby paving the way for monitoring CAR T cells in solid tumors.
Insights
Researchers developed a method to track CAR T cells in tumors using iron oxide nanoparticles and advanced imaging techniques. This breakthrough enables noninvasive monitoring of CAR T-cell therapy for metastatic osteosarcoma.
Area of Science:
- Oncology
- Immunotherapy
- Biomedical Imaging
Background:
- Metastatic osteosarcoma has a poor prognosis, necessitating novel therapeutic strategies.
- Chimeric antigen receptor (CAR) T-cell therapy shows promise but faces challenges in solid tumors, particularly in monitoring T-cell accumulation.
- Current clinical imaging techniques are insufficient for tracking CAR T cells within solid tumors.
Purpose of the Study:
- To develop a clinically translatable method for labeling CAR T cells with iron oxide nanoparticles.
- To enable noninvasive monitoring of CAR T cells in solid tumors using multimodal imaging.
- To evaluate the efficacy of iron oxide nanoparticle-labeled CAR T cells in tracking tumor homing.
Main Methods:
- CAR T cells were labeled with iron oxide nanoparticles (ferumoxytol) using a microfluidics device via mechanoporation.
- Nanoparticle uptake was optimized to preserve T-cell proliferation, viability, and function.
- Multimodal imaging, including MRI, photoacoustic imaging (PAT), and magnetic particle imaging (MPI), was employed to detect labeled T cells.
Main Results:
- Successful labeling of CAR T cells with ferumoxytol was achieved, maintaining T-cell function.
- Multimodal imaging demonstrated the homing of iron-labeled T cells to osteosarcoma tumors and off-target sites in animal models.
- Unlabeled T cells were not visualized, confirming the specificity of the imaging technique.
Conclusions:
- The developed method allows for the noninvasive monitoring of CAR T cells in solid tumors.
- This approach using ferumoxytol-labeled CAR T cells and multimodal imaging is a significant advancement for CAR T-cell therapy in oncology.
- This technique paves the way for improved efficacy assessment and clinical translation of CAR T-cell therapies for metastatic osteosarcoma.
