Document Detail


Imaging of genetically engineered T cells by PET using gold nanoparticles complexed to Copper-64.
MedLine Citation:
PMID:  23034721     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (64)Cu(2+) using the macrocyclic chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTA) and polyethyleneglycol (GNP-(64)Cu/PEG2000). MicroPET/CT was used to visualize CAR(+)EGFPffLucHyTK(+)GNP-(64)Cu/PEG2000(+) T cells and correlated with bioluminescence imaging. These data demonstrate that GNPs conjugated with (64)Cu(2+) can be prepared as a radiotracer for PET and used to image T cells using an approach that has translational implications.
Authors:
Parijat Bhatnagar; Zheng Li; Yoonsu Choi; Jianfeng Guo; Feng Li; Daniel Y Lee; Matthew Figliola; Helen Huls; Dean A Lee; Tomasz Zal; King C Li; Laurence J N Cooper
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Integrative biology : quantitative biosciences from nano to macro     Volume:  5     ISSN:  1757-9708     ISO Abbreviation:  Integr Biol (Camb)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-17     Completed Date:  2013-06-24     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  101478378     Medline TA:  Integr Biol (Camb)     Country:  England    
Other Details:
Languages:  eng     Pagination:  231-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Tracking / methods*
Copper Radioisotopes / diagnostic use*
Genetic Engineering / methods
Gold / diagnostic use*
Metal Nanoparticles / diagnostic use*
Mice
Positron-Emission Tomography / methods*
Radiopharmaceuticals / diagnostic use
T-Lymphocytes / physiology*,  radionuclide imaging*
Grant Support
ID/Acronym/Agency:
CA16672/CA/NCI NIH HHS; P01 CA148600/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS; R01 CA120956/CA/NCI NIH HHS; R01 CA124782/CA/NCI NIH HHS; R01 CA124782/CA/NCI NIH HHS; R01 CA137059/CA/NCI NIH HHS; R01 CA141303/CA/NCI NIH HHS; R33 CA116127/CA/NCI NIH HHS; U54 CA143837/CA/NCI NIH HHS; U54CA 143837/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Copper Radioisotopes; 0/Radiopharmaceuticals; 7440-57-5/Gold
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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