title: Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography.
abstract: We have incorporated a positron emission tomography (PET) functionality in T cells expressing a CD19-specific chimeric antigen receptor (CAR) to non-invasively monitor the adoptively transferred cells.
  
  
  
  We engineered T cells to express CD19-specific CAR, firefly luciferase (ffLuc), and herpes simplex virus type-1 thymidine kinase (TK) using the non-viral-based Sleeping Beauty (SB) transposon/transposase system adapted for human application. Electroporated primary T cells were propagated on CD19+artificial antigen-presenting cells.
  
  
  
  After 4 weeks, 90 % of cultured cells exhibited specific killing of CD19+targets in vitro, could be ablated by ganciclovir, and were detected in vivo by bioluminescent imaging and PET following injection of 2'-deoxy-2'-[18F]fluoro-5-ethyl-1-β-D-arabinofuranosyl-uracil ([18F]FEAU).
  
  
  
  This is the first report demonstrating the use of SB transposition to generate T cells which may be detected using PET laying the foundation for imaging the distribution and trafficking of T cells in patients treated for B cell malignancies.
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Amer M
authors.initials: AM
authors.lastname: Najjar
authors.affiliation: Melanoma Medical Oncology-Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Pallavi R
authors.initials: PR
authors.lastname: Manuri
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Olivares
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Flores
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Tiejuan
authors.initials: T
authors.lastname: Mi
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Huls
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Molecular Imaging Program, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
authors.forename: Nashaat
authors.initials: N
authors.lastname: Turkman
authors.affiliation: Center for Advanced Biomedical Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Paolillo
authors.affiliation: Melanoma Medical Oncology-Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Roszik
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Rabinovich
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.|The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Lee
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mian
authors.initials: M
authors.lastname: Alauddin
authors.affiliation: Molecular Imaging Program, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
authors.forename: Juri
authors.initials: J
authors.lastname: Gelovani
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. ljncooper@mdanderson.org.|Ziopharm Oncology Inc., Boston, MA, USA. ljncooper@mdanderson.org.
authors.forename: Laurence J N
authors.initials: LJ
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000737:chemistry; D002460:Cell Line; D015774:Ganciclovir / Q000494:pharmacology; D018014:Gene Transfer Techniques; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D013937:Thymidine Kinase / Q000378:metabolism*; D019076:Transgenes; D019895:Transposases / Q000378:metabolism*; D014981:Xenopus
chemical_list: C508411:2'-fluoro-2'-deoxy-5-fluoroethyl-1-beta-D-arabinofuranosyl uracil; C000605956:CD19-specific chimeric antigen receptor; D019275:Radiopharmaceuticals; D011948:Receptors, Antigen, T-Cell; D001086:Arabinofuranosyluracil; D008156:Luciferases; D013937:Thymidine Kinase; D019895:Transposases; D015774:Ganciclovir
keywords: B cell malignancy; Chimeric antigen receptor; Immunotherapy