Imaging CAR T Cells with a Dual Function PET Reporter Gene

Michael D. Farwell, MD

Research

In vivo cell-tracking methods are needed to noninvasively monitor the presence, distribution, quantity, and viability of the administered CAR T cells. A novel approach to in vivo cell tracking, which overcomes some of the limitations of the currently available reporter genes, involves the use of the mutant human FK506 binding protein, F36V-FKBP, as a dual function reporter-suicide gene, since it has a number of high affinity ligands that could serve as novel PET radiotracers, and it has been successfully utilized in humans as a component of the iCasp9 suicide gene. Dr. Farwell set out to test a radiolabeled derivative of a ligand with high affinity for the mutant protein F36V-FKBP and negligible affinity for the wild-type FKBP protein, as a novel PET radiotracer for imaging CAR T cells (and other cell-based therapies) that contain the dual function reporter-suicide gene F36V-FKBP as a component of iCasp9. His group is also developing a modified iCasp9 dual function reporter-suicide gene in which the ligand binding domain (F36V-FKBP) has been replaced by E. coli dihydrofolate reductase (eDHFR).

Biography

Dr. Michael Farwell received his MD from Columbia University and is board-certified in Diagnostic Radiology and Nuclear Medicine.  He is currently an Assistant Professor of Radiology at the Perelman School of Medicine at the University of Pennsylvania.