Molecular Imaging (Jul 2009)

Repetitive Noninvasive Monitoring of HSV1-tk-Expressing T Cells Intravenously Infused into Nonhuman Primates Using Positron Emission Tomography and Computed Tomography with F-FEAU

  • Gianpietro Dotti,
  • Mei Tian,
  • Barbara Savoldo,
  • Amer Najjar,
  • Laurence J.N. Cooper,
  • James Jackson,
  • Amanda Smith,
  • Osama Mawlawi,
  • Rajesh Uthamanthil,
  • Agatha Borne,
  • David Brammer,
  • Vincenzo Paolillo,
  • Mian Alauddin,
  • Carlos Gonzalez,
  • David Steiner,
  • William K. Decker,
  • Frank Marini,
  • Steven Kornblau,
  • Catherine M. Bollard,
  • Elizabeth J. Shpall,
  • Juri G. Gelovani

DOI
https://doi.org/10.2310/7290.2009.00022
Journal volume & issue
Vol. 8

Abstract

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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 [ 18 F]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil ( 18 F-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 18 F-FEAU PET-CT imaging for monitoring the distribution of intravenously administered sr39HSV1-tk gene-transduced CTLs in humans.