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

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 adoptive...

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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: SAGE Publications 2009-07-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2009.00022
Description
Summary: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.
ISSN:1536-0121