Sensitive methodologies for tracking Tumor Infiltrating Lymphocyte immunotherapy by MRI

Background & Aim Cancer immunotherapies have made a great progress, have demonstrated encouraging clinical results, and hold much promise in the treatment of cancer. As we target solid tumors with immunotherapies, the hurdle of being able to select a suitable target and achieve successful cellular delivery/homing to the site of disease remains. With this in mind, being able to visualize a rapidly dividing cellular population is another obstacle to consider. Here we demonstrate the application of two clinically applicable perfluorocarbon (PFC) tracers, one commercially available and a next-generation magnetic resonance imaging (MRI) probe called FETRIS. Both of these agents enable the migration and persistence of cellular therapies to be noninvasively imaged by 19F MRI, while the FETRIS reagent enhances detection sensitivity. Methods, Results & Conclusion Here we validate the use of these labels on TIL preparations and donor T cells. We show that adding the cellular label does not alter the viability or release characteristics of cells and generated IND enabling data sets for both reagents. By pairing the PFC signal with conventional proton MRI from the same imaging session, the images are able to be overlaid, allowing cells to be traced to their anatomical location. With nominal exogenous fluorine naturally present in tissue, labeled cells appear with little background. Images of both reagents show the detection and sensitivity of the method and how they can be applied to monitor the distribution of cells over time.