title: Repetitive noninvasive monitoring of HSV1-tk-expressing T cells intravenously infused into nonhuman primates using positron emission tomography and computed tomography with 18F-FEAU.
abstract: Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) has been successfully used to treat patients with different types of cancer. However, the long-term spatial-temporal dynamics of the distribution of systemically infused CTLs remains largely unknown. Noninvasive imaging of adoptively transferred CTLs using molecular-genetic reporter imaging with positron emission tomography and computed tomography (PET-CT) represents an innovative approach to understanding the long-term migratory patterns and therapeutic potential of adoptively transferred T cells. Here we report the application of repetitive PET-CT imaging with [18F]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil (18F-FEAU) in two nonhuman primates demonstrating that autologous polyclonal macaque T lymphocytes activated and transduced with a retroviral vector encoding for the sr39 mutant herpes simplex virus 1 thymidine kinase (sr39HSV1-tk) reporter gene can be detected after intravenous infusion in discrete lymphoid organs and in sites of inflammation. This study represents a proof of principle and supports the application of 18F-FEAU PET-CT imaging for monitoring the distribution of intravenously administered sr39HSV1-tk gene-transduced CTLs in humans.
authors.affiliation: Department of Experimental Diagnostic Imaging, The University of Texas, USA.
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
authors.forename: Mei
authors.initials: M
authors.lastname: Tian
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.forename: Amer
authors.initials: A
authors.lastname: Najjar
authors.forename: Laurence J N
authors.initials: LJ
authors.lastname: Cooper
authors.forename: James
authors.initials: J
authors.lastname: Jackson
authors.forename: Amanda
authors.initials: A
authors.lastname: Smith
authors.forename: Osama
authors.initials: O
authors.lastname: Mawlawi
authors.forename: Rajesh
authors.initials: R
authors.lastname: Uthamanthil
authors.forename: Agatha
authors.initials: A
authors.lastname: Borne
authors.forename: David
authors.initials: D
authors.lastname: Brammer
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Paolillo
authors.forename: Mian
authors.initials: M
authors.lastname: Alauddin
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez
authors.forename: David
authors.initials: D
authors.lastname: Steiner
authors.forename: William K
authors.initials: WK
authors.lastname: Decker
authors.forename: Frank
authors.initials: F
authors.lastname: Marini
authors.forename: Steven
authors.initials: S
authors.lastname: Kornblau
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Juri G
authors.initials: JG
authors.lastname: Gelovani
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002478:Cells, Cultured; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D017930:Genes, Reporter; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D011323:Primates; D013601:T-Lymphocytes / Q000378:metabolism* / Q000637:transplantation*; D013937:Thymidine Kinase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D005462:Fluorine Radioisotopes; D001086:Arabinofuranosyluracil; C054103:2'-fluoro-5-ethylarabinosyluracil; D013937:Thymidine Kinase