Repetitive noninvasive monitoring of HSV1-tk-expressing T cells intravenously infused into nonhuman primates using positron emission tomography and computed tomography with 18F-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 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.
Dotti
Gianpietro
G
Department of Experimental Diagnostic Imaging, The University of Texas, USA.
Tian
Mei
M
Savoldo
Barbara
B
Najjar
Amer
A
Cooper
Laurence J N
LJ
Jackson
James
J
Smith
Amanda
A
Mawlawi
Osama
O
Uthamanthil
Rajesh
R
Borne
Agatha
A
Brammer
David
D
Paolillo
Vincenzo
V
Alauddin
Mian
M
Gonzalez
Carlos
C
Steiner
David
D
Decker
William K
WK
Marini
Frank
F
Kornblau
Steven
S
Bollard
Catherine M
CM
Shpall
Elizabeth J
EJ
Gelovani
Juri G
JG
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
D005462:Fluorine Radioisotopes; D001086:Arabinofuranosyluracil; C054103:2'-fluoro-5-ethylarabinosyluracil; D013937:Thymidine Kinase