Repetitive noninvasive monitoring of HSV1-tk-expressing T cells intravenously infused into nonhuman primates using positron emission tomography and computed tomography with 18F-FEAU

Mol Imaging. Jul-Aug 2009;8(4):230-7.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • Arabinofuranosyluracil / analogs & derivatives*
  • Arabinofuranosyluracil / pharmacokinetics
  • Cells, Cultured
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Genes, Reporter
  • Herpesvirus 1, Human / genetics*
  • Herpesvirus 1, Human / metabolism
  • Infusions, Intravenous
  • Macaca mulatta
  • Male
  • Monitoring, Immunologic / methods
  • Positron-Emission Tomography / methods
  • Primates
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / transplantation*
  • Thymidine Kinase / analysis
  • Thymidine Kinase / genetics*
  • Thymidine Kinase / metabolism
  • Tomography, X-Ray Computed / methods

Substances

  • Fluorine Radioisotopes
  • Arabinofuranosyluracil
  • 2'-fluoro-5-ethylarabinosyluracil
  • Thymidine Kinase