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Issue 1, 2013
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Imaging of genetically engineered T cells by PET using gold nanoparticles complexed to Copper-64

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Abstract

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.

Graphical abstract: Imaging of genetically engineered T cells by PET using gold nanoparticles complexed to Copper-64

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Publication details

The article was received on 23 Apr 2012, accepted on 17 Sep 2012 and first published on 18 Sep 2012


Article type: Technical Innovation
DOI: 10.1039/C2IB20093G
Citation: Integr. Biol., 2013,5, 231-238
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    Imaging of genetically engineered T cells by PET using gold nanoparticles complexed to Copper-64

    P. Bhatnagar, Z. Li, Y. Choi, J. Guo, F. Li, D. Y. Lee, M. Figliola, H. Huls, D. A. Lee, T. Zal, K. C. Li and L. J. N. Cooper, Integr. Biol., 2013, 5, 231
    DOI: 10.1039/C2IB20093G

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