Adoptive transfer of primary T cells genetically modified to have desired specificity can exert an anti-tumor response in some patients. To improve our understanding of their therapeutic potential we have developed a clinically-appealing approach to reveal their in vivo biodistribution using nanoparticles that serve as a radiotracer for imaging by positron emission tomography (PET). T cells electroporated with DNA plasmids from the Sleeping Beauty transposon–transposase system to co-express a chimeric antigen receptor (CAR) specific for CD19 and Firefly luciferase (ffLuc) were propagated on CD19+ K562-derived artificial antigen presenting cells. The approach to generating our clinical-grade CAR+ T cells was adapted for electro-transfer of gold nanoparticles (GNPs) functionalized with 64Cu2+ using the macrocyclic chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTA) and polyethyleneglycol (GNP–64Cu/PEG2000). MicroPET/CT was used to visualize CAR+EGFPffLucHyTK+GNP–64Cu/PEG2000+ T cells and correlated with bioluminescence imaging. These data demonstrate that GNPs conjugated with 64Cu2+ can be prepared as a radiotracer for PET and used to image T cells using an approach that has translational implications.
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