Repetitive Noninvasive Monitoring of HSV1-tk-Expressing T Cells Intravenously Infused into Nonhuman Primates Using Positron Emission Tomography and Computed Tomography with 18F-FEAU
- Resource Type
- Authors
- Dotti, Gianpietro; Tian, Mei; Savoldo, Barbara; Najjar, Amer; Cooper, Laurence J.N.; Jackson, James; Smith, Amanda; Mawlawi, Osama; Uthamanthil, Rajesh; Borne, Agatha; Brammer, David; Paolillo, Vincenzo; Alauddin, Mian; Gonzalez, Carlos; Steiner, David; Decker, William K.; Marini, Frank; Kornblau, Steven; Bollard, Catherine M.; Shpall, Elizabeth J.; Gelovani, Juri G.
- Source
- Subject
- Male
Primates
Fluorine Radioisotopes
T-Lymphocytes
Arabinofuranosyluracil
Herpesvirus 1, Human
Adoptive Transfer
Macaca mulatta
Thymidine Kinase
Article
Genes, Reporter
Monitoring, Immunologic
Positron-Emission Tomography
Animals
Female
Infusions, Intravenous
Tomography, X-Ray Computed
Cells, Cultured
- Language
- English
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.