Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography.

Abstract

T cells genetically engineered to express chimeric antigen receptors (CAR) have shown unprecedented results in pivotal clinical trials for patients with B cell malignancies or multiple myeloma (MM). However, numerous obstacles limit the efficacy and prohibit the widespread use of CAR T cell therapies due to poor trafficking and infiltration into tumor sites as well as lack of persistence in vivo. Moreover, life-threatening toxicities, such as cytokine release syndrome or neurotoxicity, are major concerns. Efficient and sensitive imaging and tracking of CAR T cells enables the evaluation of T cell trafficking, expansion, and in vivo characterization and allows the development of strategies to overcome the current limitations of CAR T cell therapy. This paper describes the methodology for incorporating the sodium iodide symporter (NIS) in CAR T cells and for CAR T cell imaging using [18F]tetrafluoroborate-positron emission tomography ([18F]TFB-PET) in preclinical models. The methods described in this protocol can be applied to other CAR constructs and target genes in addition to the ones used for this study.

• Authors: Reona Sakemura, Michelle J Cox, Aditya Bansal, Claudia Manriquez Roman, Mehrdad Hefazi, Cynthia J Vernon, Dianna L Glynn, Mukesh K Pandey, Timothy R DeGrado, Elizabeth L Siegler, Saad S Kenderian
• Journal: Journal of visualized experiments : JoVE (J Vis Exp) Issue 180 (02 17 2022) ISSN: 1940-087X [Electronic] United States
• PMID: 35253798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Video-Audio Media)

Chemical References

• Receptors, Antigen, T-Cell
• Receptors, Chimeric Antigen

Topics

• Humans
• Immunotherapy, Adoptive (methods)
• Multiple Myeloma (diagnostic imaging, therapy)
• Positron Emission Tomography Computed Tomography (methods)
• Receptors, Antigen, T-Cell (genetics)
• Receptors, Chimeric Antigen (genetics)
• T-Lymphocytes